Abnormalities of endocrine function in patients with clinically silent adrenal masses.
Abstract
Ambrosi B, Peverelli S, Passini E, Re T, Ferrario R, Colombo P, Sartorio A, Faglia G. Abnormalities of endocrine function in patients with clinically "silent" adrenal masses. Eur J Endocrinol 1995;132:422–8. ISSN 0804–4643 Because, in recent years, patients with incidentally discovered adrenal masses have been encountered increasingly, their endocrine function was investigated in basal conditions and after dynamic tests. Thirty-two patients (23 women and 9 men, aged 28–74 years) were studied. Lesion diameter, as documented by computed tomography and/or nuclear magnetic resonance imaging, ranged between 5 and 65 mm; the tumors were localized on the right in 22 patients, on the left in 5 and bilaterally in 5 cases. In basal conditions, urinary free cortisol (UFC) excretion, plasma adrenocorticotropin (ACTH) and cortisol levels were normal, except for 4 patients who showed high UFC and ACTH levels in the low–normal range. Ovine corticotropin-releasing hormone (CRH, 1 μg/kg iv) was given to 18 patients, inducing normal ACTH and cortisol responses in 12, blunted responses in 4 and no response in 2 cases. No reduction in ACTH and cortisol levels after suppression tests was observed in 4 of 29 patients after dexamethasone (1 mg overnight) or in 6 of 29 after loperamide. The 4 patients who were unresponsive to both tests did not show any further inhibition after high-dose dexamethasone administration, had low plasma ACTH levels and showed impaired or absent responses to the CRH test: they were diagnosed as affected with preclinical Cushing's syndrome. An exogenous ACTH test performed in 30 patients caused a normal cortisol rise. Basal mean 17-hydroxyprogesterone (17-OHP) levels were not different from those in normal subjects. After ACTH the 17-OHP rate increase was higher than in normal subjects (17-OHP(30–)/30 min = 0.31 ±0.04 vs 0.07 ± 0.01 nmol·1−1·min−1; mean±SEM, p < 0.01); in particular, this parameter was elevated in 18 of 30 patients (17-OHP(30–0)/30 min range = 0.23–1.07 vs 0.01–0.19 nmol·1−1·min−1 in normal subjects). In a subset of 11 patients, serum markers of bone (bone-GLA protein (BGP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and collagen turnover (aminoterminal propeptide of type III procollagen (PIIINP)) were significantly (p < 0.01) lower than in normal subjects: in particular, in 2 preclinical Cushing's patients they were markedly reduced and rose after unilateral adrenalectomy. Of these 2 patients who underwent surgery, 1 showed a secondary hypoadrenalism. The histological study in 7 operated patients revealed the presence of benign adenoma in 4 cases and carcinoma, myelolipoma and hematoma in the others. In conclusion, in patients with incidentalomas endocrine testing is recommended because about two-thirds of them show subtle signs of adrenal overactivity. In patients with enzymatic defects of steroidogenesis a surgical approach is not suggested. On the contrary, the existence of a preclinical Cushing's syndrome has to be investigated carefully and followed up in order to disclose the possible appearance of clinical and/or metabolic features induced by the hypercortisolism and to suggest a surgical treatment. B Ambrosi, Institute of Endocrine Sciences, Ospedale Maggiore, IRCCS, via F Sforza 35, 20122 Milan, Italy
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Determining ACTH levels after CRH does not add any advantage to screening for subclinical hypercortisolism.
“The determination of ACTH levels after CRH does not seem to add any advantage (1,23,34,35,37,38,46) to screening for SH.”
From Diagnosis and Treatment of Subclinical Hypercortisolism (2011) · cites this paper as [37]
Other authors used the simultaneous presence of at least two altered HPA axis parameters for diagnosing subclinical hypercortisolism.
“To simplify the diagnostic workout, other authors used the concomitant presence of at least two altered parameters of HPA axis activity for SH diagnosis (9, 18, 19, 21, 32, 37, 39, 40, 42, 47, 49, 52-54, 56, 60, 61).”
From Diagnosis and Treatment of Subclinical Hypercortisolism (2011) · cites this paper as [37]
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“7 69 0 6 Ambrosi 1995 (53) Italy 32 67 2–6.”
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“Ambrosi et al. 1995 (51) 32 2.5 55 2.7 12.5 0 0 3.13 0 78.1 Aso & Homma 1992 (16) 210 0.7 53 4.9 3.3 23.3 3.3 4.29 1.4 36.7 Bardet et al. 1996 (52) 46 NR NR 2.6 6.5 4.4 0 4.35 2.2 69.6 Barzon et al. 2002 (53) 284 1.5 56 3.6 11.3 5.9 2.1 8.80 2.8 64.8 Bastounis et al. 1997 (54) 86 1.5 61 4.1 3.5…”
InfluentialAME Position Statement on adrenal incidentaloma
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“The determination of ACTH levels after CRH does not seem to add any advantage (1, 23, 34, 35, 37, 38, 46) to screening for SH.”
BackgroundInfluentialLong-term follow-up study of patients with adrenal incidentalomas.
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“As previously reported ( 6 , 9, 10), SCS was defined by the absence of signs or symptoms of hypercortisolism and by the presence of at least two of the following criteria: inadequate cortisol inhibition after 1 mg dexamethasone (cortisol levels $ 138 nmol/l), high or high – normal UFC excretion ($ 275 nmol/24 h), low…”
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“The appropriate management of patients with subclinical Cushing’s syndrome remains controversial (Reincke et al., 1992; Osellaet al., 1994; Ambrosi et al., 1995; Klooset al., 1995) in the absence of clear proof of the detrimental effects, if any, of silent hypercortisolism.”
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Self-citationGlucocorticoids and neuroendocrine function
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“Secondly, in the case of surgical removal of the mass, perioperative cortisol replacement therapy is recommended to avoid the risk of adrenal insufficiency due to suppression of the contralateral normal gland (3, 6, 9, 11 ).”
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Self-citationBiochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas.
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MANAGEMENT APPROACHES TO ADRENAL INCIDENTALOMAS
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Subclinical Cushing's syndrome.
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“levels have also frequently been described in patients with adrenal incidentalomas and, in fact many authors have suggested that low DHEAS levels represent the most common abnormality in such patients (Osella et al., 1994; Ambrosi et al., 1995; Flecchiaet al., 1995).”
BackgroundSubclinical Cushing's syndrome in adrenal incidentalomas
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Subclinical Cushing's syndrome
Terzolo, M., Bovio, S., Pia, A. R., Osella, G., Borretta, G., Angeli, A., & Reimondo, G. (2007) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302007000800013 · Cited by 67 · see citing works
“Increase in UFC excretion has been less frequently found [ 7 ,8,12,14,15] in agreement with the view that measurement of UFC has insufficient sensitivity to detect mild hypercortisolism [18].”
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Primary aldosteronism in normokalemic patients with adrenal incidentalomas
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Bone metabolism and mass in women with Cushing’s syndrome and adrenal incidentaloma
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“…decreased ACTH responsiveness to CRH and excessive urinary cortisol excretion have been detected with a decreasing order of frequency (Virkkala et al., 1989; Jockenhovel et al., 1992; Reincke et al., 1992; Osella et al., 1994; Ambrosi et al., 1995; Flecchia et al., 1995; Kasperlik-Zaluska, 1997).”
BackgroundMethodInfluentialEvaluation of hormonal function in a series of incidentally discovered adrenal masses.
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Subclinical Cushing’s syndrome
Leo, M. D., Cozzolino, A., Colao, A. A. L., & Pivonello, R. (2012) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2012.02.001 · Cited by 63 · see citing works
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Clinical Study of Adrenal Incidentaloma in Korea
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“2% in the largest clinical study) varies greatly depending on the diagnostic criteria and the screening methods used (3-5,18,20).”
BackgroundMethodInfluentialAdipokine levels and cardiovascular risk in patients with adrenal incidentaloma
Ermetici, F., Malavazos, A. E., Corbetta, S., Morricone, L. F., Dall’Asta, C., Romanelli, M. M. C., & Ambrosi, B. (2007) · Metabolism · doi:10.1016/j.metabol.2006.12.018 · Cited by 59 · see citing works
Self-citationOsella, G., Reimondo, G., Peretti, P., Alì, A., Paccotti, P., Angeli, A., & Terzolo, M. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.2.7178 · Cited by 54 · see citing works
“Different endocrine protocols were used to explore the function of the HPA axis in the literature, but most researchers suggest that two or more abnormalities should be present to define a truly relevant hypercortisolemic state (7, 9, 26, 33).”
MethodThe natural history of incidentally discovered adrenocortical adenomas: a retrospective evaluation.
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Ahn, S. H., Kim, J. H., Baek, S. H., Kim, H., Cho, Y. Y., Suh, S., Kim, B.-J., Hong, S., Koh, J.-M., Lee, S. H., et al. (2018) · Yonsei Medical Journal · doi:10.3349/ymj.2018.59.4.501 · Cited by 43 · see citing works
“Moreover, recent research has focused on subclinically hyperfunctional AIs showing a mild increase in hormone levels without other signs and symptoms of relevant diseases, since these conditions can eventually influence morbidity and mortality.(4,5) Accordingly, several study groups have sought to establish clinical p…”
Incidentally discovered adrenal masses
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1,161 patients with adrenal incidentalomas: indications for surgery
Kasperlik-Zaluska, A. A., Otto, M., Cichocki, A. S., Rosłonowska, E., Slowinska-Srzednicka, J., Zgliczyński, W., Jeske, W., Papierska, L., Tołłoczko, T., Polański, J., et al. (2007) · Langenbeck s Archives of Surgery · doi:10.1007/s00423-007-0238-6 · Cited by 38 · see citing works
“By definition, the patients with AI should not present any signs of hormone excess; however, detailed clinical, biochemical, and hormonal examinations could reveal some subtle abnormalities, named subclinical adrenal hyperfunction [7].”
BackgroundKann, P., Laudes, M., Piepkorn, B., Heintz, A., & Beyer, J. (2001) · Clinical Rheumatology · doi:10.1007/s100670170099 · Cited by 34 · see citing works
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“In recent years, the existence of several alterations of hormonal secretion in patients with ‘silent’ adrenal masses has been documented. Either subtle abnormalities in steroid biosynthesis or abnormal cortisol regulation leading to a ‘subclinical’ Cushing’s syndrome can be detected. Particularly, low dehydroepiandros…”
BackgroundSelf-citationLaparoscopic Adrenal Surgery: New Frontiers
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Metabolism of glucocorticoids and mineralocorticoids in patients with adrenal incidentalomas
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“Some incidental adrenal adenomas show a functional autonomy even if the entity of hypercortisolism is relatively mild, because the patients do not present with a Cushingoid habit (5, 7, 8, 27 ).”
BackgroundMANAGEMENT APPROACHES TO ADRENAL INCIDENTALOMAS (ADRENALOMAS)
Linos, D. A. (2000) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70121-3 · Cited by 29 · see citing works
Biochemical bone turnover markers in hormonal disorders in adults: a narrative review
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Preclinical Cushing’s syndrome: Report of seven cases and a review of the literature
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17-hydroxyprogesterone response to ACTH in bilateral and monolateral adrenal incidentalomas
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The clinical evaluation of silent adrenal masses
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“Incidental adrenal adenomas occur in 4% of patients undergoing abdominal imaging and 5–20% of these individuals have biochemical hypercortisolism [78–86].”
BackgroundSubclinical Cushing's syndrome in adrenal incidentalomas--possible metabolic consequences.
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Self-citation
- Authors
- Ambrosi, B., Peverelli, S., Passini, E., Re, T., Ferrario, R., Colombo, P., Sartorio, A., & Faglia, G.
- Affiliations
- University of Milan (IT)
- Corresponding author
- Ambrosi, Bruno
- ORCID
- Colombo, Paolo
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 1995-04
- Volume
- 132
- Issue
- 4
- Pages
- 422-428
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2050960639
- Cited by
- 136
- References
- 0
- Citations by year
- 2024: 2 · 2023: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 15.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- adrenal incidentaloma, preclinical Cushing's syndrome, endocrine function, ACTH, cortisol, dexamethasone suppression test, CRH stimulation test, 17-hydroxyprogesterone, Cushing's disease, adrenocortical function, adrenal insufficiency
- MeSH terms
- Adrenal Gland Neoplasms, Adrenal Glands, Adrenalectomy, Adrenocorticotropic Hormone, Adult, Aged, Androstenedione, Bone and Bones, Collagen, Corticotropin-Releasing Hormone, Cushing Syndrome, Diagnosis, Differential, Female, Humans, Hydrocortisone, Hydroxyprogesterones, Magnetic Resonance Imaging, Male, Middle Aged, Peptide Fragments, Procollagen, Radioimmunoassay, Tomography, X-Ray Computed, Osteocalcin, 17-alpha-Hydroxyprogesterone
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