Management of Adrenocortical Carcinoma

Bruno Allolio; Stefanie Hahner; Dirk Weismann; Martin Fassnacht


Clin Endocrinol. 2004;60(3) 

In This Article

Clinical Presentation

Functioning ACC (approximately 60% of cases) often presents with signs and symptoms of adrenal steroid hormone excess, although hypersecretion of androgens in males or oestrogens in females may go unnoticed. The same holds true for hypersecretion of steroid precursors (e.g. 17-α-hydroxy-progesterone; deoxycorticosterone) which is frequently detectable in seemingly nonfunctioning tumours. Cushing's syndrome (CS) with or without virilization is the most frequent presentation in functioning ACC (Didolkar et al., 1981; Pommier & Brennan, 1992; Wajchenberg et al., 2000; Favia et al., 2001; Icard et al., 2001). Rapid development of CS with skin atrophy, muscle weakness, hyperglycaemia, hypertension and psychiatric symptoms is common. Androgen excess in women leads to hirsutism, male pattern baldness, deepening voice, breast atrophy and menstrual abnormalities. The anabolic action of concomitantly secreted androgens may counteract the glucocorticoid-induced muscle atrophy. Oestrogen-secreting ACCs in males usually present with gynaecomastia and testicular atrophy, in women breast tenderness and irregular menstrual bleeding may occur (Schteingart & Homan, 2001). Aldosterone hypersecretion in ACC is rare and may lead to hypokalaemia and hypertension which may also occur in severe adrenal CS with massive hypercortisolaemia, leading to incomplete renal inactivation by 11β-dehydrogenase type II and hence mineralocorticoid excess (Stewart et al., 1995). In children, adrenal sex steroid excess is common and may lead to virilization and precocious pseudo-puberty (Ribeiro et al., 2000; Wajchenberg et al., 2000). Due to low efficiency in steroid production, clinical abnormalities may be subtle in a significant percentage of patients.

Patients with a nonfunctioning ACC usually present with symptoms related to the local mass effect like abdominal fullness, pain, indigestion, nausea and vomiting (Samaan & Hickey, 1987; Pommier & Brennan, 1992; Dackiw et al., 2001). In a minority of patients, weight loss, low-grade fever and weakness may also occur (Bodie et al., 1989; Kasperlik-Zaluska et al., 1998). Due to the large tumour size at diagnosis, an abdominal mass may be palpable in a significant percentage of patients. The initial manifestation may also be related to metastatic disease (e.g. pathologic fracture, bone pain). A substantial and apparently increasing fraction of patients is diagnosed incidentally by abdominal imaging (Icard et al., 1992; Kasperlik-Zaluska et al., 1998).

A peculiar finding in ACC is in our experience a low prevalence of nonspecific tumour symptoms (e.g. anorexia, weight loss) even in the presence of a large tumour burden. This absence of a systemic inflammatory response may contribute to the late diagnosis in many patients with ACC.