Congenital adrenal hyperplasia presenting as a large adrenal incidentaloma in an elderly man
A 65‐year‐old phenotypically male presented with lower urinary tract symptoms. On examination, he was noted to have an empty scrotum and small penile length (Fig. 1).
To look for intra‐abdominal testes, abdominal computed tomography showed a 5.8 × 3.9 × 4.5 cm right adrenal incidentalomas (AI), diffusely thickened bilateral adrenal glands, but no intraperitoneal testes. However, a uterine‐like structure with bilateral small ovaries and a prostate gland were identified (Fig. 2).
The patient was raised as a man since birth but recalled having corrective surgery in childhood and can stand to void afterwards. He had short stature (height 143 cm, weight 39 kg, body mass index 19 kg/m2).
Hormonal studies to evaluate catecholamine, cortisol and aldosterone excess, were negative, ruling out pheochromocytoma, cortisol‐producing tumour and hyperaldosteronism as Conn's adenoma, respectively.
Serum sex hormones were measured because of ambiguous genitalia. Testosterone level was normal; oestradiol and 17‐hydroxyprogesterone were markedly raised, suggesting congenital adrenal hyperplasia (CAH). Urinary steroid profiling showed elevated steroid metabolites upstream of the enzymatic action of 21‐hydroxylase. Genetic analysis confirmed CAH due to 21‐hydroxylase deficiency (21OHD), with compound heterozygous p.Ile172Asn, p.Arg483Pro and p.Met485Trpfs*56 mutations in the CYP21A2 gene at chromosome 6p21.3.
Because of the malignancy risk in adrenal mass greater than 4 cm, laparoscopic right adrenalectomy and bilateral salpingo‐oophorectomy were performed. Intra‐operative findings revealed a 6 cm right vascular adrenal tumour weighed 59 g, post‐menopausal uterus and bilateral ovaries in the presence of hydrosalpinx.
Histopathological examination revealed adrenocortical hyperplasia with mild cytological atypia and gonadal dysgenesis.
No long‐term hormone replacement was required and the patient remained well 8 months post‐operatively.
A chromosome test eventually identified the patient to be genetically female with 46, XX karyotype.
The frequency of AI increases with age from <1% in children to 4% at 50 years and to about 15% in individuals over 70 years old.1
CAH is an uncommon cause of AI. The estimated carrier frequency of CAH is 1–2%.2 Approximately 90–95% of all CAH cases is due to 21OHD, characterized by impaired cortisol synthesis and varied aldosterone productions, shunting the accumulating steroid precursors to adrenal androgen production.
Many patients with mild 21OHD may never be diagnosed, while those with severe disease can present with ambiguous genitalia and cortisol deficiency in childhood (‘classic’ CAH) with salt‐wasting or simple virilizing phenotype. Others may not have cortisol deficiency (‘non‐classic’ CAH) but present with hyperandrogenism similar to that of polycystic ovarian syndrome.
The American Association of Clinical Endocrinologists/American Association of Endocrine Surgeons guidelines recommend diagnostic work‐up for CAH in patients with AI in the presence of clinically suggestive features or bilateral masses.3 The oldest case of 21OHD reported in the literature was an 88‐year‐old woman presented with a 3 × 4 × 5 cm adrenal incidentaloma,2 prompting clinical signs and symptoms of CAH to be considered in all ages.
A 10‐year retrospective review of all suspected CAH cases presented as AI identified nine patients with a mean age of 54 ± 19 years at presentation. Two‐thirds were female, and 4/6 women had symptoms of hyperandrogenism. The majority had multiple bilateral tumours, with a median diameter of 1.5 (1.0–8.0) cm. All were non‐functioning adenoma, and no case of adrenocortical carcinoma (ACC) was diagnosed.2
Adrenal tumours up to 2 cm in size were reported frequently in 21OHD adults.4 Adrenal myelolipomas and testicular adrenal rest tumours were common adrenal lesions found in males with 21OHD, and adrenocortical hyperplasia in both sexes.
The question remained whether adrenalectomy is required for these lesions. ACC was regarded as rare in the context of 21OHD, except for a few reported cases of classic 21OHD.5 Kacem et al.