Testicular Adrenal Rest Tumour

Testicular adrenal rest tumours are benign, non-malignant nodules of ectopic adrenal cortical tissue within the testis. They occur mainly in men with congenital adrenal hyperplasia, where chronically high ACTH drives their growth.

They are found in about 20 to 50% of adult men with congenital adrenal hyperplasia, with a reported range of 14 to 94%. They may appear in childhood and are usually bilateral.

They cause obstructive damage to the testis and are a common cause of infertility and hypogonadism in these men.

Pathophysiology. During development, adrenal cells travel with the gonad and may remain near the rete testis. The cells carry receptors for ACTH, angiotensin II and LH, and enlarge under high ACTH when glucocorticoid control is poor.

The growing masses compress the seminiferous tubules and rete testis, causing obstruction, tubular damage, reduced sperm production and Leydig cell failure.

Underlying conditions:

• Congenital adrenal hyperplasia from 21-hydroxylase deficiency (about 95% of cases) or 11-beta-hydroxylase deficiency.
• Rare: Nelson syndrome after bilateral adrenalectomy for Cushing disease, and other conditions with chronic ACTH excess.

Often no symptoms. Firm, irregular, bilateral nodules near the hilum may be palpable, with normal or small testes. Oligozoospermia or azoospermia, low testosterone, and rarely pain. History of congenital adrenal hyperplasia, salt wasting, early virilisation, short stature, or poor adherence to steroid replacement.

Adrenal crisis (vomiting, hypotension, hypoglycaemia, hyponatraemia and hyperkalaemia) may occur in salt wasting disease during illness, and needs emergency hydrocortisone.

• Scrotal ultrasound: bilateral, multifocal, lobulated, hypoechoic lesions near the mediastinum testis, from 2 mm to several centimetres, with prominent vascularity on Doppler and sometimes microlithiasis.
• MRI: lesions isointense or hypointense on T1 and T2, with strong enhancement. It helps when ultrasound is inconclusive.
• Hormones: ACTH, 17-hydroxyprogesterone, androstenedione, testosterone, LH, FSH, renin and electrolytes.
• AFP, beta-hCG and lactate dehydrogenase, which are normal.
• Semen analysis, and bone density in hypogonadism.
• Biopsy or frozen section at exploration only when the lesion is unilateral, the patient has no known congenital adrenal hyperplasia, there is rapid growth, or markers are raised.

Differential diagnosis.

• Leydig cell tumour
• Seminoma and other germ cell tumours
• Testicular lymphoma
• Sertoli cell tumour
• Orchitis, haematoma or infarct
• Metastasis

• Optimise glucocorticoid replacement to suppress ACTH without over treating.
  • Adults: hydrocortisone 15 to 25 mg orally daily in 2 or 3 divided doses (the largest in the morning), or prednisolone 3 to 5 mg daily in 1 or 2 doses, or dexamethasone 0.25 to 0.5 mg at night. Children: hydrocortisone 10 to 15 mg/m2 daily in 3 divided doses.
  • Fludrocortisone 0.05 to 0.2 mg orally once daily in salt wasting disease, titrated to renin and blood pressure.
  • Short courses of higher dose dexamethasone (0.25 to 0.75 mg daily) may shrink early lesions, with close monitoring for Cushingoid change, weight gain, bone loss and glucose intolerance.
• Stress dosing: double or triple the daily dose during fever or illness. Adrenal crisis: hydrocortisone 100 mg intravenously or intramuscularly (children 50 mg/m2, or 25 mg under 3 years, 50 mg at 3 to 12 years), with intravenous 0.9% saline and glucose.
• Fertility: sperm banking in adolescence or early adulthood, assisted conception with intracytoplasmic sperm injection, and testicular sperm extraction in azoospermia.
• Testis sparing enucleation for pain, rapid growth, diagnostic doubt, or refractory obstruction. Fertility seldom returns after surgery.
• Testosterone replacement for confirmed deficiency when fertility is not wanted: gel 50 mg daily or testosterone undecanoate 1000 mg intramuscularly at 0 and 6 weeks then every 10 to 14 weeks, titrated to a mid-normal level.
• Radiotherapy and orchidectomy are not needed for benign disease.

Monitoring. Hormone profile every 3 to 6 months, and ultrasound every 1 to 2 years from adolescence or earlier. Semen analysis yearly when fertility is wanted. Bone density every 2 to 3 years in adults.

Referral and escalation. Refer to endocrinology (paediatric, then adult) and urology or andrology. Urgent referral for adrenal crisis, or a solitary rapidly growing lesion.