ACTH adenomas transforming their clinical expression: Report of 5 cases

Matteo Zoli, Marco Faustini-Fustini, Diego Mazzatenta, Gianluca Marucci, Eugenio De Carlo, Antonella Bacci, Ernesto Pasquini, Giuseppe Lanzino, Giorgio Frank

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Object Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon . Methods The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. Results Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18-51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma "shifted" to a functioning adenoma and then regressed back to a silent form with spontaneous resolution of Cushing disease. This patient again developed hypercortisolism, which finally resolved spontaneously. In this series, the transformation occurred after a mean of 3.5 years (range 6 months to 7 years). The shift from an ACTH-silent to a functioning adenoma was observed in 9% of the ACTH-silent adenomas in this series (4 of 44 cases), and the spontaneous remission of Cushing disease to a silent corticotroph cell adenoma occurred in 1.5% of cases of this series (2 of 132 functioning ACTH adenomas). At follow-up (mean 107 months; range 60-177 months), cortisol levels were within normal limits in all 5 cases. However, 1 patient required Gamma Knife radiosurgery and eventually adrenalectomy for disease control to be achieved. Conclusions The ability of silent ACTH adenomas to transform their secretion pattern poses a challenge for neurosurgeons and endocrinologists. Because the transformation is often unexpected, the clinical and biochemical data can be underestimated. Furthermore, this bizarre and unpredictable postoperative tumor behavior can lead to misinterpretation of clinical and endocrinological outcomes. Even if these cases are very rare, they are not anecdotal in large series. Thus, ACTH adenomas require careful biohumoral and neuroradiological follow-up to detect possible transformations.

Original languageEnglish (US)
Article number15
JournalNeurosurgical Focus
Volume38
Issue number2
DOIs
StatePublished - 2015

Fingerprint

Adenoma
Adrenocorticotropic Hormone
Pituitary ACTH Hypersecretion
Cushing Syndrome
Pituitary Neoplasms
Neoplasms
ACTH-Secreting Pituitary Adenoma
Spontaneous Remission
Radiosurgery
Adrenalectomy
Brain
Dexamethasone
Hydrocortisone

Keywords

  • Cushing disease
  • Endoscopic endonasal surgery
  • Hypercortisolism
  • Radiosurgery
  • Silent ACTH pituitary adenoma

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Medicine(all)

Cite this

Zoli, M., Faustini-Fustini, M., Mazzatenta, D., Marucci, G., De Carlo, E., Bacci, A., ... Frank, G. (2015). ACTH adenomas transforming their clinical expression: Report of 5 cases. Neurosurgical Focus, 38(2), [15]. https://doi.org/10.3171/2014.11.FOCUS14679

ACTH adenomas transforming their clinical expression : Report of 5 cases. / Zoli, Matteo; Faustini-Fustini, Marco; Mazzatenta, Diego; Marucci, Gianluca; De Carlo, Eugenio; Bacci, Antonella; Pasquini, Ernesto; Lanzino, Giuseppe; Frank, Giorgio.

In: Neurosurgical Focus, Vol. 38, No. 2, 15, 2015.

Research output: Contribution to journalArticle

Zoli, M, Faustini-Fustini, M, Mazzatenta, D, Marucci, G, De Carlo, E, Bacci, A, Pasquini, E, Lanzino, G & Frank, G 2015, 'ACTH adenomas transforming their clinical expression: Report of 5 cases', Neurosurgical Focus, vol. 38, no. 2, 15. https://doi.org/10.3171/2014.11.FOCUS14679
Zoli M, Faustini-Fustini M, Mazzatenta D, Marucci G, De Carlo E, Bacci A et al. ACTH adenomas transforming their clinical expression: Report of 5 cases. Neurosurgical Focus. 2015;38(2). 15. https://doi.org/10.3171/2014.11.FOCUS14679
Zoli, Matteo ; Faustini-Fustini, Marco ; Mazzatenta, Diego ; Marucci, Gianluca ; De Carlo, Eugenio ; Bacci, Antonella ; Pasquini, Ernesto ; Lanzino, Giuseppe ; Frank, Giorgio. / ACTH adenomas transforming their clinical expression : Report of 5 cases. In: Neurosurgical Focus. 2015 ; Vol. 38, No. 2.
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abstract = "Object Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon . Methods The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. Results Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18-51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma {"}shifted{"} to a functioning adenoma and then regressed back to a silent form with spontaneous resolution of Cushing disease. This patient again developed hypercortisolism, which finally resolved spontaneously. In this series, the transformation occurred after a mean of 3.5 years (range 6 months to 7 years). The shift from an ACTH-silent to a functioning adenoma was observed in 9{\%} of the ACTH-silent adenomas in this series (4 of 44 cases), and the spontaneous remission of Cushing disease to a silent corticotroph cell adenoma occurred in 1.5{\%} of cases of this series (2 of 132 functioning ACTH adenomas). At follow-up (mean 107 months; range 60-177 months), cortisol levels were within normal limits in all 5 cases. However, 1 patient required Gamma Knife radiosurgery and eventually adrenalectomy for disease control to be achieved. Conclusions The ability of silent ACTH adenomas to transform their secretion pattern poses a challenge for neurosurgeons and endocrinologists. Because the transformation is often unexpected, the clinical and biochemical data can be underestimated. Furthermore, this bizarre and unpredictable postoperative tumor behavior can lead to misinterpretation of clinical and endocrinological outcomes. Even if these cases are very rare, they are not anecdotal in large series. Thus, ACTH adenomas require careful biohumoral and neuroradiological follow-up to detect possible transformations.",
keywords = "Cushing disease, Endoscopic endonasal surgery, Hypercortisolism, Radiosurgery, Silent ACTH pituitary adenoma",
author = "Matteo Zoli and Marco Faustini-Fustini and Diego Mazzatenta and Gianluca Marucci and {De Carlo}, Eugenio and Antonella Bacci and Ernesto Pasquini and Giuseppe Lanzino and Giorgio Frank",
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journal = "Neurosurgical Focus",
issn = "1092-0684",
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TY - JOUR

T1 - ACTH adenomas transforming their clinical expression

T2 - Report of 5 cases

AU - Zoli, Matteo

AU - Faustini-Fustini, Marco

AU - Mazzatenta, Diego

AU - Marucci, Gianluca

AU - De Carlo, Eugenio

AU - Bacci, Antonella

AU - Pasquini, Ernesto

AU - Lanzino, Giuseppe

AU - Frank, Giorgio

PY - 2015

Y1 - 2015

N2 - Object Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon . Methods The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. Results Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18-51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma "shifted" to a functioning adenoma and then regressed back to a silent form with spontaneous resolution of Cushing disease. This patient again developed hypercortisolism, which finally resolved spontaneously. In this series, the transformation occurred after a mean of 3.5 years (range 6 months to 7 years). The shift from an ACTH-silent to a functioning adenoma was observed in 9% of the ACTH-silent adenomas in this series (4 of 44 cases), and the spontaneous remission of Cushing disease to a silent corticotroph cell adenoma occurred in 1.5% of cases of this series (2 of 132 functioning ACTH adenomas). At follow-up (mean 107 months; range 60-177 months), cortisol levels were within normal limits in all 5 cases. However, 1 patient required Gamma Knife radiosurgery and eventually adrenalectomy for disease control to be achieved. Conclusions The ability of silent ACTH adenomas to transform their secretion pattern poses a challenge for neurosurgeons and endocrinologists. Because the transformation is often unexpected, the clinical and biochemical data can be underestimated. Furthermore, this bizarre and unpredictable postoperative tumor behavior can lead to misinterpretation of clinical and endocrinological outcomes. Even if these cases are very rare, they are not anecdotal in large series. Thus, ACTH adenomas require careful biohumoral and neuroradiological follow-up to detect possible transformations.

AB - Object Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon . Methods The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. Results Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18-51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma "shifted" to a functioning adenoma and then regressed back to a silent form with spontaneous resolution of Cushing disease. This patient again developed hypercortisolism, which finally resolved spontaneously. In this series, the transformation occurred after a mean of 3.5 years (range 6 months to 7 years). The shift from an ACTH-silent to a functioning adenoma was observed in 9% of the ACTH-silent adenomas in this series (4 of 44 cases), and the spontaneous remission of Cushing disease to a silent corticotroph cell adenoma occurred in 1.5% of cases of this series (2 of 132 functioning ACTH adenomas). At follow-up (mean 107 months; range 60-177 months), cortisol levels were within normal limits in all 5 cases. However, 1 patient required Gamma Knife radiosurgery and eventually adrenalectomy for disease control to be achieved. Conclusions The ability of silent ACTH adenomas to transform their secretion pattern poses a challenge for neurosurgeons and endocrinologists. Because the transformation is often unexpected, the clinical and biochemical data can be underestimated. Furthermore, this bizarre and unpredictable postoperative tumor behavior can lead to misinterpretation of clinical and endocrinological outcomes. Even if these cases are very rare, they are not anecdotal in large series. Thus, ACTH adenomas require careful biohumoral and neuroradiological follow-up to detect possible transformations.

KW - Cushing disease

KW - Endoscopic endonasal surgery

KW - Hypercortisolism

KW - Radiosurgery

KW - Silent ACTH pituitary adenoma

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