Adrenocortical Carcinoma Associated With Lynch Syndrome

Most cases of adrenocortical carcinoma (ACC) are sporadic; however, some occur as a part of a hereditary syndrome, such as Li-Fraumeni syndrome, multiple endocrine neoplasia type 1, familial adenomatous polyposis, neurofibromatosis type 1, Beckwith-Wiedemann syndrome, or Lynch syndrome. Here we present an incidentally discovered ACC in a patient with undiagnosed Lynch syndrome.

Case Report

This 65-year-old woman was initially evaluated for postmenopausal vaginal bleeding. Transvaginal ultrasound showed endometrial thickening and several uterine fibroids, and subsequent histology demonstrated benign endometrial hyperplasia. Incidentally, on the initial ultrasound, a large right adrenal mass was noted. Subsequent computed tomography (CT) scan revealed a heterogeneous right adrenal mass, measuring 7.8 × 6.0 × 5.1 cm ( Fig. 31.1 ). The patient was referred to Mayo Clinic for further management of the adrenal mass.

On evaluation, the patient reported fatigue and a weight loss of 3 pounds over several weeks. On physical examination, her blood pressure was 135/83 mmHg and body mass index was 24.7 kg/m ² . She did not have any signs of androgen, cortisol, or aldosterone excess.

Recently, her sister was diagnosed with Lynch syndrome. Subsequently, our patient was also tested and found positive for a familial pathogenic variant in MutS homolog 6 (MSH6) . Colonoscopy, performed several months previously, was normal.

INVESTIGATIONS

Laboratory evaluation showed normal levels of 24-hour urinary metanephrine and normetanephrine but was positive for androgen precursor and androgen excess, hypercortisolism, and estrogen excess ( Table 31.1 ).

TABLE 31.1

Laboratory Tests

Biochemical Test	Result	Reference Range
Cortisol after overnight 1-mg DST, mcg/dL	13	<1.8
Cortisol, mcg/dL	14	7–21
ACTH, pg/mL	<5	7.2–63
DHEA-S, mcg/dL	403	<15–157
Androstenedione, ng/dL	151	30–200
17-Hydroxyprogesterone, ng/dL	167	<51
17-Hydroxypregnenolone, ng/dL	888	31–455
Total testosterone, ng/dL	30	8–60
Estradiol, pg/mL	113	<10 (postmenopausal)
Aldosterone, ng/dL	20	<21
Plasma renin activity, ng/mL per hour	2	≤0.6–3
24-Hour urine cortisol, mcg/24 h	68	<45
24-Hour urine metanephrine,mcg/24 h	68	<400
24-Hour urine normetanephrine, mcg/24 h	340	<900