Gonadotroph Pituitary Adenoma

Gonadotroph pituitary adenoma is a tumour of gonadotroph lineage (SF1 positive). Most are clinically non-functioning, but rare functioning tumours secrete FSH, LH or intact gonadotrophins and cause ovarian hyperstimulation, testicular enlargement or precocious puberty.

Gonadotroph tumours are about a quarter to a third of pituitary adenomas. Functioning forms are rare and recognised mostly in premenopausal women.

Most present as macroadenomas in adults over 40 years with visual symptoms or hypopituitarism.

Pathophysiology.

Autonomous FSH secretion drives ovarian follicle growth and high oestradiol in premenopausal women, with low LH and multiple large ovarian cysts. In men FSH raises testicular size with normal or low testosterone.

Compression of the normal gland and stalk causes hypopituitarism and mild hyperprolactinaemia.

• Women: heavy or irregular menses, pelvic pain, large multicystic ovaries, endometrial hyperplasia and infertility.
• Men: testicular enlargement, low libido. Children: precocious puberty.
• Mass effect: bitemporal hemianopia, headache, cranial nerve palsies, hypopituitarism.

Red flags.

• Visual loss or apoplexy.
• Severe pelvic pain suggesting ovarian torsion.

• Premenopausal woman: raised FSH with raised oestradiol and low LH, with pelvic ultrasound showing enlarged multicystic ovaries.
• Men: raised FSH with normal or low testosterone and testicular enlargement.
• Pituitary MRI with contrast, visual fields, prolactin, IGF-1, cortisol, thyroid function, and the alpha subunit. A thyrotropin releasing hormone test showing paradoxical gonadotrophin rise supports a tumour.
• Histology with SF1, FSH and LH immunostaining.

Differential diagnosis.

• Pituitary hyperplasia from primary ovarian or testicular failure (FSH high with low sex steroids and a smaller gland).
• Non-functioning adenoma with stalk effect, and prolactinoma.
• Polycystic ovary syndrome and ovarian tumours.
• Iatrogenic ovarian hyperstimulation.

• Transsphenoidal surgery for functioning tumours, compressive tumours and hypopituitarism, in a specialist pituitary centre.
• Dopamine agonists (cabergoline 0.5 to 3 mg weekly), somatostatin analogues and gonadotrophin releasing hormone analogues have inconsistent effect and are second line.
• Stereotactic radiotherapy for residual or regrowing tumour. Replace hormone deficits: hydrocortisone first (15 to 25 mg daily in two or three divided doses), then levothyroxine, then sex steroids.
• After surgery ovarian cysts regress. Check the endometrium if hyperoestrogenism has been prolonged.

Special groups. Premenopausal women: advise on fertility (ovulation can occur with high FSH), contraception and endometrial protection, and warn about ovarian torsion.

Monitoring. FSH, LH and oestradiol or testosterone and pelvic ultrasound after surgery. MRI at 3 to 6 months, then yearly. Annual pituitary function and visual fields.

Referral and escalation. Pituitary multidisciplinary team; urgent review for visual loss, apoplexy or torsion.