Table 6. Open in new tab... | Oxford Academic

Table 6.

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Sub-differentiation of bilateral adrenal incidentalomas.

	Bilateral hyperplasia	Bilateral adrenal adenomas	Two morphological similar adrenal masses (but indeterminate by imaging and hormone analysis)	Two morphological different adrenal masses
Imaging work-up	There are 2 main forms of hyperplasia, a diffuse type without distinct nodules and a macronodular type, in which both adrenals typically harbor more than one nodule (usually with unenhanced HU < 10) and the remaining adrenals are usually thickened.	Typically, both adrenals harbor one distinct/unambiguous adenoma (unenhanced HU < 10) and the remaining adrenal limbs are normal or thin.	Unenhanced and/or enhanced HU in CT are typically similar for the different masses (as is appearance in MRI or FDG-PET) and imaging characteristics are not typical for an adenoma.	The appearance of the adrenal masses is clearly different in unenhanced and/or enhanced CT, MRI or FDG-PET, but at least one of them has characteristics not typical of an adenoma.
Hormonal work-up (in addition to standard diagnostic work-up)	If congenital adrenal hyperplasia is suspected, consider measurement of basal 17-OH progesterone to diagnose (or exclude) CAH, which may be especially important to consider in case of signs, symptoms or biochemistry of hyperandrogenemia.	In case of signs, symptoms or biochemistry of hyperandrogenemia, additional measurement of basal 17-OH progesterone should be considered to exclude CAH.	In infiltrative masses (eg, lymphomas, metastases) or bilateral hemorrhages, exclusion of adrenal insufficiency is required.	Standard hormonal work-up is sufficient (see Section 5.3).
Clinical consequences	If CAH is excluded, consider primary bilateral macronodular adrenal hyperplasia (PBMAH) as diagnosis. In the presence of multiple modules and ACTH-independent MACS, genetic testing for germline pathogenic ARMC5 variants should be offered^a. In patients with MACS, unilateral adrenalectomy of the dominant side might be considered using an individualized approach considering age, degree of cortisol excess, general conditions and patient preferences.	In patients with MACS, management should follow the recommendations given in R.3.3-9. In selected patients, unilateral adrenalectomy of the dominant lesion might be considered using an individualized approach considering age, degree of cortisol excess, general conditions and patient preferences.	In pheochromocytomas, genetic testing for PPGL-associated genes is mandatory. If malignant lesions are suspected, a biopsy should be considered.	Investigation of underlying etiology needed.

	Bilateral hyperplasia	Bilateral adrenal adenomas	Two morphological similar adrenal masses (but indeterminate by imaging and hormone analysis)	Two morphological different adrenal masses
Imaging work-up	There are 2 main forms of hyperplasia, a diffuse type without distinct nodules and a macronodular type, in which both adrenals typically harbor more than one nodule (usually with unenhanced HU < 10) and the remaining adrenals are usually thickened.	Typically, both adrenals harbor one distinct/unambiguous adenoma (unenhanced HU < 10) and the remaining adrenal limbs are normal or thin.	Unenhanced and/or enhanced HU in CT are typically similar for the different masses (as is appearance in MRI or FDG-PET) and imaging characteristics are not typical for an adenoma.	The appearance of the adrenal masses is clearly different in unenhanced and/or enhanced CT, MRI or FDG-PET, but at least one of them has characteristics not typical of an adenoma.
Hormonal work-up (in addition to standard diagnostic work-up)	If congenital adrenal hyperplasia is suspected, consider measurement of basal 17-OH progesterone to diagnose (or exclude) CAH, which may be especially important to consider in case of signs, symptoms or biochemistry of hyperandrogenemia.	In case of signs, symptoms or biochemistry of hyperandrogenemia, additional measurement of basal 17-OH progesterone should be considered to exclude CAH.	In infiltrative masses (eg, lymphomas, metastases) or bilateral hemorrhages, exclusion of adrenal insufficiency is required.	Standard hormonal work-up is sufficient (see Section 5.3).
Clinical consequences	If CAH is excluded, consider primary bilateral macronodular adrenal hyperplasia (PBMAH) as diagnosis. In the presence of multiple modules and ACTH-independent MACS, genetic testing for germline pathogenic ARMC5 variants should be offered^a. In patients with MACS, unilateral adrenalectomy of the dominant side might be considered using an individualized approach considering age, degree of cortisol excess, general conditions and patient preferences.	In patients with MACS, management should follow the recommendations given in R.3.3-9. In selected patients, unilateral adrenalectomy of the dominant lesion might be considered using an individualized approach considering age, degree of cortisol excess, general conditions and patient preferences.	In pheochromocytomas, genetic testing for PPGL-associated genes is mandatory. If malignant lesions are suspected, a biopsy should be considered.	Investigation of underlying etiology needed.

Patients with pathogenic ARMC5 variants have typically a more severe phenotype and deserve special attention.

Abbreviations: HU, Hounsfield unit; CAH, congenital adrenal hyperplasia; MACS, mild autonomous cortisol secretion.

Table 6.

Open in new tab

Sub-differentiation of bilateral adrenal incidentalomas.

	Bilateral hyperplasia	Bilateral adrenal adenomas	Two morphological similar adrenal masses (but indeterminate by imaging and hormone analysis)	Two morphological different adrenal masses
Imaging work-up	There are 2 main forms of hyperplasia, a diffuse type without distinct nodules and a macronodular type, in which both adrenals typically harbor more than one nodule (usually with unenhanced HU < 10) and the remaining adrenals are usually thickened.	Typically, both adrenals harbor one distinct/unambiguous adenoma (unenhanced HU < 10) and the remaining adrenal limbs are normal or thin.	Unenhanced and/or enhanced HU in CT are typically similar for the different masses (as is appearance in MRI or FDG-PET) and imaging characteristics are not typical for an adenoma.	The appearance of the adrenal masses is clearly different in unenhanced and/or enhanced CT, MRI or FDG-PET, but at least one of them has characteristics not typical of an adenoma.
Hormonal work-up (in addition to standard diagnostic work-up)	If congenital adrenal hyperplasia is suspected, consider measurement of basal 17-OH progesterone to diagnose (or exclude) CAH, which may be especially important to consider in case of signs, symptoms or biochemistry of hyperandrogenemia.	In case of signs, symptoms or biochemistry of hyperandrogenemia, additional measurement of basal 17-OH progesterone should be considered to exclude CAH.	In infiltrative masses (eg, lymphomas, metastases) or bilateral hemorrhages, exclusion of adrenal insufficiency is required.	Standard hormonal work-up is sufficient (see Section 5.3).
Clinical consequences	If CAH is excluded, consider primary bilateral macronodular adrenal hyperplasia (PBMAH) as diagnosis. In the presence of multiple modules and ACTH-independent MACS, genetic testing for germline pathogenic ARMC5 variants should be offered^a. In patients with MACS, unilateral adrenalectomy of the dominant side might be considered using an individualized approach considering age, degree of cortisol excess, general conditions and patient preferences.	In patients with MACS, management should follow the recommendations given in R.3.3-9. In selected patients, unilateral adrenalectomy of the dominant lesion might be considered using an individualized approach considering age, degree of cortisol excess, general conditions and patient preferences.	In pheochromocytomas, genetic testing for PPGL-associated genes is mandatory. If malignant lesions are suspected, a biopsy should be considered.	Investigation of underlying etiology needed.

	Bilateral hyperplasia	Bilateral adrenal adenomas	Two morphological similar adrenal masses (but indeterminate by imaging and hormone analysis)	Two morphological different adrenal masses
Imaging work-up	There are 2 main forms of hyperplasia, a diffuse type without distinct nodules and a macronodular type, in which both adrenals typically harbor more than one nodule (usually with unenhanced HU < 10) and the remaining adrenals are usually thickened.	Typically, both adrenals harbor one distinct/unambiguous adenoma (unenhanced HU < 10) and the remaining adrenal limbs are normal or thin.	Unenhanced and/or enhanced HU in CT are typically similar for the different masses (as is appearance in MRI or FDG-PET) and imaging characteristics are not typical for an adenoma.	The appearance of the adrenal masses is clearly different in unenhanced and/or enhanced CT, MRI or FDG-PET, but at least one of them has characteristics not typical of an adenoma.
Hormonal work-up (in addition to standard diagnostic work-up)	If congenital adrenal hyperplasia is suspected, consider measurement of basal 17-OH progesterone to diagnose (or exclude) CAH, which may be especially important to consider in case of signs, symptoms or biochemistry of hyperandrogenemia.	In case of signs, symptoms or biochemistry of hyperandrogenemia, additional measurement of basal 17-OH progesterone should be considered to exclude CAH.	In infiltrative masses (eg, lymphomas, metastases) or bilateral hemorrhages, exclusion of adrenal insufficiency is required.	Standard hormonal work-up is sufficient (see Section 5.3).
Clinical consequences	If CAH is excluded, consider primary bilateral macronodular adrenal hyperplasia (PBMAH) as diagnosis. In the presence of multiple modules and ACTH-independent MACS, genetic testing for germline pathogenic ARMC5 variants should be offered^a. In patients with MACS, unilateral adrenalectomy of the dominant side might be considered using an individualized approach considering age, degree of cortisol excess, general conditions and patient preferences.	In patients with MACS, management should follow the recommendations given in R.3.3-9. In selected patients, unilateral adrenalectomy of the dominant lesion might be considered using an individualized approach considering age, degree of cortisol excess, general conditions and patient preferences.	In pheochromocytomas, genetic testing for PPGL-associated genes is mandatory. If malignant lesions are suspected, a biopsy should be considered.	Investigation of underlying etiology needed.

Patients with pathogenic ARMC5 variants have typically a more severe phenotype and deserve special attention.

Abbreviations: HU, Hounsfield unit; CAH, congenital adrenal hyperplasia; MACS, mild autonomous cortisol secretion.