PET imaging of adrenal glands

Adrenal glands

Adrenal glands (suprarenal glands) are endocrine organs above the kidneys, consisting of the steroid hormone producing cortex and the catecholamine producing medulla. Renal fascia is a fatty layer of connective tissue that surrounds both the kidney and adrenal gland. There is only a thin wall of connective tissue between the kidney and adrenal gland.

In healthy subjects, each adrenal gland is ∼5×3×1 cm in size and weighs ∼4-5 g. Adrenal cortex makes up about 90-92% of the mass, although it is only about 1 mm thick. Cortex consists of three zone: glomerulosa (15% of cortical mass), fasciculata (70-80%), and reticularis (5-15%). Zona glomerulosa synthesizes mineralocorticoids (mainly aldosterone), Zona fasciculata produces glucocorticoids (cortisol, corticosterone, 11-deoxycorticosterone), and Zona reticularis produces androgens (DHEA, DHEA-S, androstenedione). Cells in zona fasciculata contain high amounts of lipids, while zona glomerulosa is very fat poor. This affects the imaging of adrenal glands, and tumours of adrenal origin.

The adrenal medulla synthesizes catecholamines (adrenaline/epinephrine and noradrenaline/norepinephrine). Adrenal medulla and sympathetic nervous system form the sympathoadrenal system, which interacts with thyroid hormones.

Accessory adrenal tissue is sometimes found in the abdominal cavity, or even fused with other organs. These glands seldom contain medulla.

Aldosterone is secreted from the adrenal zona glomerulosa in response to hyperkalemia or angiotensin II. Aldosterone binds to mineralocorticoid receptors, and in the renal late distal convoluted tubules, connecting tubules, and collecting ducts this enhances Na⁺ reabsorption by the epithelial sodium channel.

The precursor for aldosterone and other corticoids is cholesterol. Adrenal function and steroid synthesis can be assessed with [¹³¹I]I-6β-iodomethyl-norcholesterol (NP-59) SPECT or [¹⁸F]FNP-59 PET (Brooks et al., 2022).

Cortical adenomas

Cortical adenomas are benign neoplasms that can arise from any of the cortical layers, leading to overproduction of the corresponding hormones. For example, Cushing's syndrome and aldosterenoma can be caused by cortical adenoma. [¹¹C]Metomidate PET can detect primary aldosteronism and cortical adenoma in difficult cases where CT/MRI and adrenal venous sampling methods fail (Powlson et al, 2015; Wong et al., 2016; Oyang et al., 2017). Due to the short halflife of ¹¹C, several ¹⁸F-labelled metomidate analogues have been developed (Wadsak et al., 2006; Erlandsson et al., 2009; Bongarzone et al., 2019; Silins et al., 2023). These and [¹¹C]metomidate bind (inhibit) both steroid 11β-hydroxylase (mitochondrial cytochrome P450 11B1, CYP11B1) and aldosterone synthase (hydroxylase cytochrome P450, CYT11B2). PET radiopharmaceuticals that are specific to aldosterone synthase, that is only expressed in zona glomerulosa, include [¹⁸F]CDP2230 (Abe et al., 2016) and [¹⁸F]AldoView (Sander et al., 2021).

Adrenal incidentalomas

Abdominal imaging for reasons not related to adrenal function leads to incidental discoveries of lesions in up to 5% of cases. These mass lesions are asymptomatic, and usually of cortical origin.

Adrenal cysts and pseudocysts are relatively common. Cysts are fibrotic, haemorrhagic tissue, possibly with chronic inflammation.

[¹⁸F]FDG can be used in differentiating benign from malignant lesions. Tumours arising from the adrenal cortex can be detected using specific tracers such as [¹¹C]metomidate (Minn et al., 2004; Hahner et al., 2011).

Pheochromocytomas

Pheochromocytomas are very rare tumours, arising from the medulla. Tumours are usually found inside the adrenal glands (intra-adrenal paragangliomas), but sometimes also elsewhere (extra-adrenal paraganglioma). Adrenal medulla synthesizes dopamine. These tumours and their metastases can be detected using for example [¹⁸F]fluorodopamine, [¹⁸F]FDOPA (Amodru et al., 2018), [¹¹C]HED (Sundin, 2016), and [⁶⁸Ga]DOTANOC (Sharma et al., 2014).

Caveats

Intravenous administration of PET radiopharmaceutical requires the puncture of blood vessel, which sometimes induces a vasovagal reaction (VVR). Otomi et al. (2016) confirmed that this will lead to increased bilateral [¹⁸F]FDG uptake in the adrenal glands.

Literature

Blake MA, Boland GWL: Adrenal Imaging. Humana Press, 2009. doi: 10.1007/978-1-59745-560-2.

Flück CE, Miller WL (eds.): Disorders of the Human Adrenal Cortex. Karger, 2008. ISBN 978–3–8055–8580–4.

Gross MD, Avram A, Fig LM, Fanti S, Al-Nahhas A, Rubello D. PET in the diagnostic evaluation of adrenal tumors. Q J Nucl Med Mol Imaging 2007; 51(3): 272-283. PMID: 17464268.

Hahner S, Sundin A. Metomidate-based imaging of adrenal masses. Horm Cancer 2011; 2(6): 348-353. doi: 10.1007/s12672-011-0093-3.

Kumar R, Alavi A, Fanti S. Adrenocortical positron emission tomography/PET-CT imaging. PET Clin. 2008; 2(3): 331-339. doi: 10.1016/j.cpet.2008.04.002.

Linos D, van Heered JA (eds.): Adrenal Glands - Diagnostic Aspects and Surgical Therapy. Springer, 2005. ISBN 3-540-41099-6. doi: 10.1007/b138213.

Minn H, Salonen A, Friberg J, Roivainen A, Viljanen T, Långsjö J, Salmi J, Välimäki M, Någren K, Nuutila P. Imaging of adrenal incidentalomas with PET using ¹¹C-metomidate and ¹⁸F-FDG. J Nucl Med 2004; 45:972–979. PMID: 15181132.

Sundin A. Adrenal molecular imaging. Front Horm Res. 2016; 45: 70-79. doi: 10.1159/000442317.

Wong KK, Miller BS, Viglianti BL, Dwamena BA, Gauger PG, Cook GJ, Colletti PM, Rubello D, Gross MD. Molecular imaging in the management of adrenocortical cancer - a systematic review. Clin Nucl Med. 2016; 41(8): e368-e382. doi: 10.1097/RLU.0000000000001112.

Tags: Adrenal glands, Adrenaline, Noradrenaline, Catecholamines, Aldosterone, Cortisol, Steroids, Autonomic nervous system

Updated at: 2023-02-03
Created at: 2017-10-07
Written by: Vesa Oikonen