Histopathological and genetic characterization of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion: a case series

Fallo, Francesco; Castellano, Isabella; Gómez-Sánchez, Celso E.; Rhayem, Yara; Pilon, Catia; Vicennati, Valentina; Santini, Donatella; Maffeis, Valeria; Fassina, Ambrogio; Mulatero, Paolo; Beuschlein, Felix; Reincke, Martín

doi:10.1007/s12020-017-1295-4

Cited by 22 publications

(20 citation statements)

References 65 publications

(82 reference statements)

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“…As cells in the zona fasciculata of the adrenal gland are known to produce cortisol in the cytoplasm, immunostaining for cortisol in each group was evaluated by technicians blinded to sample grouping. Three sections were randomly selected for cell counting [43,44].…”

Section: Immunohistochemistrymentioning

confidence: 99%

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation

Shida¹,

Ikeda²,

Tani³

et al. 2020

PLoS ONE

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We previously showed that postmortem serum levels of adrenocorticotropic hormone (ACTH) were significantly higher in cases of hypothermia (cold exposure) than other causes of death. This study examined how the human hypothalamic-pituitary-adrenal axis, and specifically cortisol, responds to hypothermia. Human samples: Autopsies on 205 subjects (147 men and 58 women; age 15-98 years, median 60 years) were performed within 3 days of death. Cause of death was classified as either hypothermia (cold exposure, n = 14) or noncold exposure (controls; n = 191). Cortisol levels were determined in blood samples obtained from the left and right cardiac chambers and common iliac veins using a chemiluminescent enzyme immunoassay. Adrenal gland tissues samples were stained for cortisol using a rabbit anti-human polyclonal antibody. Cell culture: AtT20, a mouse ACTH secretory cell line, and Y-1, a corticosterone secretory cell line derived from a mouse adrenal tumor, were analyzed in mono-and co-culture, and times courses of ACTH (in AtT20) and corticosterone (in Y-1) secretion were assessed after low temperature exposure mimicking hypothermia and compared with data for samples collected postmortem for other cases of death. However, no correlation between ACTH concentration and cortisol levels was observed in hypothermia cases. Immunohistologic analyses of samples from hypothermia cases showed that cortisol staining was localized primarily to the nucleus rather than the cytoplasm of cells in the zona fasciculata of the adrenal gland. During both mono-culture and coculture, AtT20 cells secreted high levels of ACTH after 10-15 minutes of cold exposure, whereas corticosterone secretion by Y-1 cells increased slowly during the first 15-20 minutes of cold exposure. Similar to autopsy results, no correlation was detected between ACTH levels and corticosterone secretion, either in mono-culture or co-culture experiments. These results suggested that ACTH-independent cortisol secretion may function as a stress response during cold exposure.

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Section: Immunohistochemistrymentioning

confidence: 99%

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation

Shida¹,

Ikeda²,

Tani³

et al. 2020

PLoS ONE

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Section: Methodsmentioning

confidence: 99%

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation

Shida

Ikeda

Tani

et al. 2019

Preprint

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2We previously showed that postmortem serum levels of adrenocorticotropic hormone 3 (ACTH) were significantly higher in cases of hypothermia (cold exposure) than other 4 causes of death. This study examined how the human hypothalamic-pituitary-adrenal axis, 5 and specifically cortisol, responds to hypothermia. Human samples: Autopsies on 205 6 subjects (147 men and 58 women; age 15-98 years, median 60 years) were performed 7 within 3 days of death. Cause of death was classified as either hypothermia (cold exposure, 8 n=14) or non-cold exposure (controls; n=191). Cortisol levels were determined in blood 9 samples obtained from the left and right cardiac chambers and common iliac veins using 10 a chemiluminescent enzyme immunoassay. Adrenal gland tissue samples were stained 11 for cortisol using a rabbit anti-human polyclonal antibi. Cell culture: AtT20, a mouse 12 ACTH secretory cell line, and Y-1, a corticosterone secretory cell line derived from a 13 mouse adrenal tumor, were analyzed in mono-and co-culture, and times courses of ACTH 14 (in AtT20) and corticosterone (in Y-1) secretion were assessed after low temperature 15 exposure mimicking hypothermia and compared with data for samples collected 16 postmortem for other causes of death. However, no correlation between ACTH 17 concentration and cortisol levels was observed in hypothermia cases. Immunohistologic 18 analyses of samples from hypothermia cases showed that cortisol staining was localized 19 primarily to the nucleus rather than the cytoplasm of cells in the zona fasciculata of the 20 adrenal gland. During both mono-culture and co-culture, AtT20 cells secreted high levels 21 of ACTH after 10-15 minutes of cold exposure, whereas corticosterone secretion by Y-1 22 cells increased slowly during the first 15-20 minutes of cold exposure. Similar to autopsy 23 results, no correlation was detected between ACTH levels and corticosterone secretion, 24 either in mono-culture or co-culture experiments. These results suggested that ACTH-25 independent cortisol secretion may function as a stress response during cold exposure. 26 27 31 etiologies of hypothermia include drug abuse, dementia, malnutrition, and infectious 32 disease, only a few studies have specifically examined pathologic findings after cold 33 exposure [8,9], especially from a biochemical perspective, such as the presence and levels 34 of ketone bodies [10-13]. Furthermore, only a few reports have estimated hormone levels 35 as part of the pathophysiologic findings of cold exposure [14-16]. 36The primary stress response system is the sympathetic/adrenomedullary (S/A) 37 system, which includes the chromogranin A [14] and hypothalamic-pituitary-adrenal 38 (HPA) axis [16, 18]. Previous studies have suggested that postmortem serum 39 adrenocorticotropic hormone (ACTH) concentration is a useful biomarker of death due 40 to cold exposure and the magnitude of physical stress responses during cold exposure 41 [17]. Increased serum concentrations of ACTH associated with activation of the HPA axis 42 and S...

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“…The cosecretion was highlighted biochemically, by the increased levels of several glucocorticoid precursors in urine samples, and clinically, by the onset of adrenal insufficiency after surgery. In a recent case series, the immunohistochemical analysis of five tumors associated with ACS and concomitant primary aldo steronism revealed that those tumors were mainly composed by zona fasciculatalike cells, with a heterogeneous expression of CYP11B1 and CYP11B2 [25]. A recent study investigating the serum steroid profiling by mass spectrometry in patients with different subtypes of Cushing's syndrome showed increased levels of 11de oxycortisol and 11deoxycorticosterone in adrenaldependent hy percortisolism, when compared to controls [26].…”

Section: Risk Of Cardiovascular Diseasesmentioning

confidence: 99%

Adrenal Incidentaloma: Picking out the High-Risk Patients

Dalmazi

2018

Exp Clin Endocrinol Diabetes

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Patients with adrenal incidentalomas and autonomous cortisol secretion (ACS) have been recognized as a category at risk of developing cardiovascular and metabolic co-morbidities. Considering the increasing number of patients affected by this condition, it is important to perform an accurate subtyping of the patients, in the light of a tailored treatment. This review aims to identify the phenotypic characteristics of patients with adrenal incidentalomas and ACS who are at risk of developing severe cortisol-related co-morbidities. ACS has been associated with severe alteration of the cardiovascular profile, including hypertension, diabetes, and atherosclerosis. Moreover, ACS has been identified as a contributing factor to the development of cardiovascular events and related mortality. Patients with ACS are also at risk of incident bone fractures, which occur in half of the patients independently of the bone mass density, and infectious diseases. Severity and persistence of hypercortisolism are among the main contributing factors for cardiovascular diseases and bone fractures. Moreover, progression of hypercortisolism over time and altered circadian cortisol rhythm seem to be important additional factors. The role of potential novel biomarkers is also discussed in this review.

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Histopathological and genetic characterization of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion: a case series

Cited by 22 publications

References 65 publications

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation

Cortisol levels after cold exposure are independent of adrenocorticotropic hormone stimulation

Adrenal Incidentaloma: Picking out the High-Risk Patients

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