Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Clinical manifestations and diagnosis of gonadotroph and other clinically nonfunctioning pituitary adenomas

Peter J Snyder, MD
Section Editor
David S Cooper, MD
Deputy Editor
Kathryn A Martin, MD


Most patients with pituitary adenomas present with signs and symptoms of hormone hypersecretion (eg, hyperprolactinemia, growth hormone [GH] excess, or hypercortisolism). However, 25 to 30 percent of pituitary adenomas are clinically nonfunctioning or "silent"; 80 to 90 percent of these are gonadotroph adenomas, making them the most common type of pituitary macroadenoma. Patients with clinically nonfunctioning adenomas most often present with neurologic symptoms due to mass effects, while others may be completely asymptomatic and be first detected on an imaging study done for reasons other than pituitary symptoms or disease. By the time patients present, a high percentage has biochemical evidence of hypopituitarism due to compression of normal pituitary cells by the macroadenoma.

The clinical features, evaluation, and diagnosis of clinically nonfunctioning pituitary adenomas are reviewed here. The treatment of these tumors and an overview of incidentally discovered sellar masses (pituitary incidentalomas) are discussed separately. (See "Treatment of gonadotroph and other clinically nonfunctioning adenomas" and "Incidentally discovered sellar masses (pituitary incidentalomas)".)


Pituitary adenomas are classified by their cell of origin (lactotroph, gonadotroph, somatotroph, corticotroph, and thyrotroph) and their size (microadenomas <1 cm, macroadenomas ≥1 cm). Most adenomas (65 to 70 percent) secrete an excess amount of hormone including prolactin, growth hormone (GH), corticotropin (ACTH), or thyroid-stimulating hormone (TSH). (See "Causes of hyperprolactinemia" and "Causes and clinical manifestations of acromegaly" and "Causes and pathophysiology of Cushing's syndrome" and "TSH-secreting pituitary adenomas".)

The remainder of pituitary adenomas (30 to 35 percent) are clinically nonfunctioning or "silent." Of these, 80 to 90 percent are gonadotroph adenomas [1]. There are also clinically nonfunctioning somatotroph [2,3], lactotroph, and corticotroph adenomas [4], although these are less common.

The majority of gonadotroph adenomas are clinically "silent" and difficult to identify because they are poorly differentiated and produce and secrete hormones inefficiently. The gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), consist of a common alpha subunit, and a unique beta subunit. TSH and hCG also consist of the common alpha subunit and a unique beta subunit. The hormones secreted by gonadotroph adenomas in order of decreasing frequency include: FSH, FSH-beta, alpha subunit, LH, and LH-beta [5].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jul 20, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Chaidarun SS, Klibanski A. Gonadotropinomas. Semin Reprod Med 2002; 20:339.
  2. Sakharova AA, Dimaraki EV, Chandler WF, Barkan AL. Clinically silent somatotropinomas may be biochemically active. J Clin Endocrinol Metab 2005; 90:2117.
  3. Wade AN, Baccon J, Grady MS, et al. Clinically silent somatotroph adenomas are common. Eur J Endocrinol 2011; 165:39.
  4. Ioachimescu AG, Eiland L, Chhabra VS, et al. Silent corticotroph adenomas: Emory University cohort and comparison with ACTH-negative nonfunctioning pituitary adenomas. Neurosurgery 2012; 71:296.
  5. Chamoun R, Layfield L, Couldwell WT. Gonadotroph adenoma with secondary hypersecretion of testosterone. World Neurosurg 2013; 80:900.e7.
  6. Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 2010; 72:377.
  7. Daneshdoost L, Gennarelli TA, Bashey HM, et al. Recognition of gonadotroph adenomas in women. N Engl J Med 1991; 324:589.
  8. Alexander JM, Biller BM, Bikkal H, et al. Clinically nonfunctioning pituitary tumors are monoclonal in origin. J Clin Invest 1990; 86:336.
  9. Herman V, Fagin J, Gonsky R, et al. Clonal origin of pituitary adenomas. J Clin Endocrinol Metab 1990; 71:1427.
  10. Zhang X, Horwitz GA, Heaney AP, et al. Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab 1999; 84:761.
  11. Vlotides G, Eigler T, Melmed S. Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. Endocr Rev 2007; 28:165.
  12. Ramírez C, Cheng S, Vargas G, et al. Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning pituitary adenomas: a high throughput TMA, immunohistochemical study. J Clin Endocrinol Metab 2012; 97:1745.
  13. Gejman R, Batista DL, Zhong Y, et al. Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 2008; 93:4119.
  14. Molitch ME. Nonfunctioning pituitary tumors and pituitary incidentalomas. Endocrinol Metab Clin North Am 2008; 37:151.
  15. Ferrante E, Ferraroni M, Castrignanò T, et al. Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. Eur J Endocrinol 2006; 155:823.
  16. Snyder PJ. Gonadotroph cell adenomas of the pituitary. Endocr Rev 1985; 6:552.
  17. Lam G, Mehta V, Zada G. Spontaneous and medically induced cerebrospinal fluid leakage in the setting of pituitary adenomas: review of the literature. Neurosurg Focus 2012; 32:E2.
  18. Nawar RN, AbdelMannan D, Selman WR, Arafah BM. Pituitary tumor apoplexy: a review. J Intensive Care Med 2008; 23:75.
  19. Semple PL, Jane JA Jr, Laws ER Jr. Clinical relevance of precipitating factors in pituitary apoplexy. Neurosurgery 2007; 61:956.
  20. Szabolcs I, Késmárki N, Bor K, et al. Apoplexy of a pituitary macroadenoma as a severe complication of preoperative thyrotropin-releasing hormone (TRH) testing. Exp Clin Endocrinol Diabetes 1997; 105:234.
  21. Frankart L, De Hertogh R, Donckier J, et al. [Pituitary apoplexy of a gonadotrophinoma and TRH/GnRH tests. Literature review]. Acta Clin Belg 1995; 50:163.
  22. Massoud W, Paparel P, Lopez JG, et al. Discovery of a pituitary adenoma following treatment with a gonadotropin-releasing hormone agonist in a patient with prostate cancer. Int J Urol 2006; 13:87.
  23. Guerra Y, Lacuesta E, Marquez F, et al. Apoplexy in non functioning pituitary adenoma after one dose of leuprolide as treatment for prostate cancer. Pituitary 2010; 13:54.
  24. Hall WA, Luciano MG, Doppman JL, et al. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med 1994; 120:817.
  25. Chong BW, Kucharczyk W, Singer W, George S. Pituitary gland MR: a comparative study of healthy volunteers and patients with microadenomas. AJNR Am J Neuroradiol 1994; 15:675.
  26. Ho DM, Hsu CY, Ting LT, Chiang H. The clinicopathological characteristics of gonadotroph cell adenoma: a study of 118 cases. Hum Pathol 1997; 28:905.
  27. Djerassi A, Coutifaris C, West VA, et al. Gonadotroph adenoma in a premenopausal woman secreting follicle-stimulating hormone and causing ovarian hyperstimulation. J Clin Endocrinol Metab 1995; 80:591.
  28. Christin-Maitre S, Rongières-Bertrand C, Kottler ML, et al. A spontaneous and severe hyperstimulation of the ovaries revealing a gonadotroph adenoma. J Clin Endocrinol Metab 1998; 83:3450.
  29. Välimäki MJ, Tiitinen A, Alfthan H, et al. Ovarian hyperstimulation caused by gonadotroph adenoma secreting follicle-stimulating hormone in 28-year-old woman. J Clin Endocrinol Metab 1999; 84:4204.
  30. Pentz-Vidovíc I, Skorić T, Grubisić G, et al. Evolution of clinical symptoms in a young woman with a recurrent gonadotroph adenoma causing ovarian hyperstimulation. Eur J Endocrinol 2000; 143:607.
  31. Shimon I, Rubinek T, Bar-Hava I, et al. Ovarian hyperstimulation without elevated serum estradiol associated with pure follicle-stimulating hormone-secreting pituitary adenoma. J Clin Endocrinol Metab 2001; 86:3635.
  32. Castelbaum AJ, Bigdeli H, Post KD, et al. Exacerbation of ovarian hyperstimulation by leuprolide reveals a gonadotroph adenoma. Fertil Steril 2002; 78:1311.
  33. Murata Y, Ando H, Nagasaka T, et al. Successful pregnancy after bromocriptine therapy in an anovulatory woman complicated with ovarian hyperstimulation caused by follicle-stimulating hormone-producing plurihormonal pituitary microadenoma. J Clin Endocrinol Metab 2003; 88:1988.
  34. Tashiro H, Katabuchi H, Ohtake H, et al. A follicle-stimulating hormone-secreting gonadotroph adenoma with ovarian enlargement in a 10-year-old girl. Fertil Steril 1999; 72:158.
  35. Gryngarten MG, Braslavsky D, Ballerini MG, et al. Spontaneous ovarian hyperstimulation syndrome caused by a follicle-stimulating hormone-secreting pituitary macroadenoma in an early pubertal girl. Horm Res Paediatr 2010; 73:293.
  36. Murakami T, Higashitsuji H, Yoshinaga K, et al. Management of ovarian hyperstimulation due to follicle-stimulating hormone-secreting gonadotroph adenoma. BJOG 2004; 111:1297.
  37. Sugita T, Seki K, Nagai Y, et al. Successful pregnancy and delivery after removal of gonadotrope adenoma secreting follicle-stimulating hormone in a 29-year-old amenorrheic woman. Gynecol Obstet Invest 2005; 59:138.
  38. Roberts JE, Spandorfer S, Fasouliotis SJ, et al. Spontaneous ovarian hyperstimulation caused by a follicle-stimulating hormone-secreting pituitary adenoma. Fertil Steril 2005; 83:208.
  39. Mor E, Rodi IA, Bayrak A, et al. Diagnosis of pituitary gonadotroph adenomas in reproductive-aged women. Fertil Steril 2005; 84:757.
  40. Faggiano M, Criscuolo T, Perrone L, et al. Sexual precocity in a boy due to hypersecretion of LH and prolactin by a pituitary adenoma. Acta Endocrinol (Copenh) 1983; 102:167.
  41. Ambrosi B, Bassetti M, Ferrario R, et al. Precocious puberty in a boy with a PRL-, LH- and FSH-secreting pituitary tumour: hormonal and immunocytochemical studies. Acta Endocrinol (Copenh) 1990; 122:569.
  42. Snyder PJ, Sterling FH. Hypersecretion of LH and FSH by a pituitary adenoma. J Clin Endocrinol Metab 1976; 42:544.
  43. Dahlqvist P, Koskinen LO, Brännström T, Hägg E. Testicular enlargement in a patient with a FSH-secreting pituitary adenoma. Endocrine 2010; 37:289.
  44. Karavitaki N, Thanabalasingham G, Shore HC, et al. Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma. Clin Endocrinol (Oxf) 2006; 65:524.
  45. Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011; 96:894.
  46. Papapetrou PD, Anagnostopoulos NI. A gonadotropin and alpha-subunit suppression test for the assessment of the ectopic production of human chorionic gonadotropin and its subunits after the menopause. J Clin Endocrinol Metab 1985; 60:1187.
  47. Glinoer D, De Nayer P, Robyn C, et al. Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and beta subunits, in relation to maternal thyroid stimulation during normal pregnancy. J Endocrinol Invest 1993; 16:881.
  48. Unkila-Kallio L, Tiitinen A, Alfthan H, et al. Effect of an in vitro fertilization program on serum CA 125, tumor-associated trypsin inhibitor, free beta-subunit of human chorionic gonadotropin, and common alpha-subunit of glycoprotein hormones. Fertil Steril 2000; 74:1125.
  49. Daneshdoost L, Gennarelli TA, Bashey HM, et al. Identification of gonadotroph adenomas in men with clinically nonfunctioning adenomas by the luteinizing hormone beta subunit response to thyrotropin-releasing hormone. J Clin Endocrinol Metab 1993; 77:1352.
  50. Hansen KA, Tho SP, Gomez F, McDonough PG. Nonfunctioning pituitary macroadenoma presenting with mild hyperprolactinemia and amenorrhea. Fertil Steril 1999; 72:663.
  51. Dadachanji MC, Bharucha NE, Jhankaria BG. Pituitary hyperplasia mimicking pituitary tumor. Surg Neurol 1994; 42:397.
  52. Samaan NA, Stepanas AV, Danziger J, Trujillo J. Reactive pituitary abnormalities in patients with Klinefelter's and Turner's syndromes. Arch Intern Med 1979; 139:198.
  53. Snyder PJ, Bashey HM, Kim SU, Chappel SC. Secretion of uncombined subunits of luteinizing hormone by gonadotroph cell adenomas. J Clin Endocrinol Metab 1984; 59:1169.