2.1.3 TSHomas

Suggested citation: The Endocrine Society. Endocrine Facts and Figures: Hypothalamic-Pituitary. First Edition. 2016

An excess of thyrotropin-releasing hormone (TSH) has been reported in 0.5-3% of pituitary tumors and can result in hyperthyroidism.92 In this type of central hyperthyroidism the TSH secretion from the pituitary tumor drives the hyperthyroidism and therefore the TSH is high or inappropriately normal in the setting of hyperthyroxinemia, and signs and symptoms of hyperthyroidism are typically present.92,93

2.1.3.1 Prevalence and Incidence

TSHomas account for 1 percent of all pituitary adenomas.94 Table 18 lists the age-standardized national prevalence and incidence of TSHomas.

Table 18. Prevalence of thyrotropin-secreting adenomas (TSHomas).
POPULATION DATA SOURCE PREVALENCE INCIDENCE REFERENCE
Hospital database Swedish university medical centers (n= 9.2 million) The Swedish Pituitary Registry and World Health Organization coding data 0.28 per 100,000 0.05 per 1 million (1990-1994)

0.26 per 1 million (2005-2009)

Onnestam et al. 201395

Abbreviations: n, number.

2.1.3.2 Life Expectancy and Mortality

A study by Sughrue et al. concluded there were not enough data to formulate an accurate SMR for TSHomas.96 Table 19 lists the treatment options for TSHomas.

2.1.3.3 Key Trends and Health Outcomes

Table 19 summarizes key therapeutic strategies for the treatment of TSHomas.

Table 19. Treatment options for thyrotropin-secreting adenomas (TSHomas).
POPULATION DATA SOURCE TREATMENT OUTCOME REFERENCE
Sweden (n=28) All Swedish university medical centers Most patients (n=22) underwent pituitary surgery, five had radiotherapy, and six had somatostatin analogues  18 patients were cured; 25% remained uncontrolled.
Subjects treated for putative primary hyperthyroidism prior
to diagnosis had TSH levels more than double those with
intact thyroid at diagnosis.
Onnestam et al. 201395
Italy (n=70)

 

 

Two tertiary referral centers in Milan, Italy

 

97% of patients were treated with surgery; in 27% of them radiotherapy was associated. 75% of patients normalized thyroid function, 58% normalized both pituitary imaging and hormonal profile, 9% developed pituitary deficiencies, and 3% had tumor or hormonal recurrence, all within the first 2 years after surgery. At last follow-up, 80% of patients normalized thyroid function, whereas 20% were currently on medical treatment. Malchiodi et al. 201497

 

Abbreviation: TSH, thyrotropin.

References

  1. Chung T, Monson J. Hypopituitarism [Updated 6 Feb 2015]. In: De Groot L, Beck-Peccoz P, Chrousos G, eds. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-
  2. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML, Endocrine S. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587-1609.
  3. Corenblum B. Hypopituitarism. 2011; http://emedicine.medscape.com/article/122287-overview – a0101. Accessed June 3 2015.
  4. Thomson Reuters, IPD Data Analytics. National Center for Health Statistics. National Hospital Discharge Survey. 2010. Accessed June 3, 2015.
  5. Regal M, Paramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol (Oxf). 2001;55(6):735-740.
  6. Fernandez-Rodriguez E, Lopez-Raton M, Andujar P, et al. Epidemiology, mortality rate and survival in a homogeneous population of hypopituitary patients. Clin Endocrinol (Oxf). 2013;78(2):278-284.
  7. Castinetti F, Reynaud R, Saveanu A, et al. [Clinical and genetic aspects of combined pituitary hormone deficiencies]. Ann Endocrinol (Paris). 2008;69(1):7-17.
  8. Castinetti F, Reynaud R, Saveanu A, Barlier A, Brue T. Genetic causes of combined pituitary hormone deficiencies in humans. Ann Endocrinol (Paris). 2012;73(2):53-55.
  9. Kelberman D, Rizzoti K, Lovell-Badge R, Robinson IC, Dattani MT. Genetic regulation of pituitary gland development in human and mouse. Endocr Rev. 2009;30(7):790-829.
  10. Takagi M, Ishii T, Inokuchi M, et al. Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism. PLoS One. 2012;7(9):e46008.
  11. de Graaff LC, Argente J, Veenma DC, Drent ML, Uitterlinden AG, Hokken-Koelega AC. PROP1, HESX1, POU1F1, LHX3 and LHX4 mutation and deletion screening and GH1 P89L and IVS3+1/+2 mutation screening in a Dutch nationwide cohort of patients with combined pituitary hormone deficiency. Horm Res Paediatr. 2010;73(5):363-371.
  12. Dateki S, Fukami M, Uematsu A, et al. Mutation and gene copy number analyses of six pituitary transcription factor genes in 71 patients with combined pituitary hormone deficiency: identification of a single patient with LHX4 deletion. J Clin Endocrinol Metab. 2010;95(8):4043-4047.
  13. Reynaud R, Gueydan M, Saveanu A, et al. Genetic screening of combined pituitary hormone deficiency: experience in 195 patients. J Clin Endocrinol Metab. 2006;91(9):3329-3336.
  14. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(8):2330-2340.
  15. Ammirati M, Wei L, Ciric I. Short-term outcome of endoscopic versus microscopic pituitary adenoma surgery: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2013;84(8):843-849.
  16. Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298(12):1429-1438.
  17. Fernandez A, Brada M, Zabuliene L, Karavitaki N, Wass JA. Radiation-induced hypopituitarism. Endocr Relat Cancer. 2009;16(3):733-772.
  18. Abu Dabrh AM, Asi N, Farah WH, et al. Radiotherapy Versus Radiosurgery in Treating Patients with Acromegaly: A Systematic Review and Meta-Analysis. Endocr Pract. 2015;21(8):943-956.
  19. Bostrom JP, Meyer A, Pintea B, et al. Risk-adapted single or fractionated stereotactic high-precision radiotherapy in a pooled series of nonfunctioning pituitary adenomas: high local control and low toxicity. Strahlenther Onkol. 2014;190(12):1095-1103.
  20. Roland Linder DKaFV. Surgery of Pituitary Tumors in Germany: Hypopituitarism, Mortality, Costs and the Effect of Surgeon. The Endocrine Society’s 94th Annual Meeting and Expo, June 23–26, 2012 – Houston, TX 2012; http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2012.NP.16.MON-718. Accessed March 15, 2016.
  21. Bates AS, Van’t Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996;81(3):1169-1172.
  22. Bulow B, Hagmar L, Mikoczy Z, Nordstrom CH, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol (Oxf). 1997;46(1):75-81.
  23. Tomlinson JW, Holden N, Hills RK, et al. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet. 2001;357(9254):425-431.
  24. Svensson J, Bengtsson BA, Rosen T, Oden A, Johannsson G. Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J Clin Endocrinol Metab. 2004;89(7):3306-3312.
  25. van Bunderen CC, van Nieuwpoort IC, Arwert LI, et al. Does growth hormone replacement therapy reduce mortality in adults with growth hormone deficiency? Data from the Dutch National Registry of Growth Hormone Treatment in adults. J Clin Endocrinol Metab. 2011;96(10):3151-3159.
  26. Gaillard RC, Mattsson AF, Akerblad AC, et al. Overall and cause-specific mortality in GH-deficient adults on GH replacement. Eur J Endocrinol. 2012;166(6):1069-1077.
  27. Pappachan JM, Raskauskiene D, Kutty VR, Clayton RN. Excess mortality associated with hypopituitarism in adults: a meta-analysis of observational studies. J Clin Endocrinol Metab. 2015;100(4):1405-1411.
  28. Burman P, Mattsson AF, Johannsson G, et al. Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality. Journal of Clinical Endocrinology & Metabolism. 2013;98(4):1466-1475.
  29. Sherlock M, Ayuk J, Tomlinson JW, et al. Mortality in patients with pituitary disease. Endocr Rev. 2010;31(3):301-342.
  30. Nielsen EH, Lindholm J, Laurberg P. Excess mortality in women with pituitary disease: a meta-analysis. Clin Endocrinol (Oxf). 2007;67(5):693-697.
  31. Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990;336(8710):285-288.
  32. Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK, Ghigo E. Hypopituitarism. Lancet. 2007;369(9571):1461-1470.
  33. Littley MD, Shalet SM, Beardwell CG, Ahmed SR, Applegate G, Sutton ML. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med. 1989;70(262):145-160.
  34. Snyder PJ, Fowble BF, Schatz NJ, Savino PJ, Gennarelli TA. Hypopituitarism following radiation therapy of pituitary adenomas. Am J Med. 1986;81(3):457-462.
  35. Cohen-Inbar O, Ramesh A, Xu Z, Vance ML, Schlesinger D, Sheehan JP. Gamma knife radiosurgery in patients with persistent acromegaly or Cushing’s disease: long-term risk of hypopituitarism. Clin Endocrinol (Oxf). 2016;84(4):524-531.
  36. Fatemi N, Dusick JR, Mattozo C, et al. Pituitary hormonal loss and recovery after transsphenoidal adenoma removal. Neurosurgery. 2008;63(4):709-718; discussion 718-709.
  37. Webb SM, Rigla M, Wagner A, Oliver B, Bartumeus F. Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. J Clin Endocrinol Metab. 1999;84(10):3696-3700.
  38. Arafah BM, Kailani SH, Nekl KE, Gold RS, Selman WR. Immediate recovery of pituitary function after transsphenoidal resection of pituitary macroadenomas. J Clin Endocrinol Metab. 1994;79(2):348-354.
  39. Aimaretti G, Ambrosio MR, Benvenga S, et al. Hypopituitarism and growth hormone deficiency (GHD) after traumatic brain injury (TBI). Growth Horm IGF Res. 2004;14 Suppl A:S114-117.
  40. Stochholm K, Gravholt CH, Laursen T, et al. Mortality and GH deficiency: a nationwide study. Eur J Endocrinol. 2007;157(1):9-18.
  41. Johannsson G, Nilsson AG, Bergthorsdottir R, et al. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metab. 2012;97(2):473-481.
  42. Attanasio AF, Bates PC, Ho KK, et al. Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status–3-year results from the HypoCCS Database. J Clin Endocrinol Metab. 2002;87(4):1600-1606.
  43. Di Iorgi N, Napoli F, Allegri AE, et al. Diabetes insipidus–diagnosis and management. Horm Res Paediatr. 2012;77(2):69-84.
  44. Maghnie M, Cosi G, Genovese E, et al. Central Diabetes Insipidus in Children and Young Adults. New England Journal of Medicine. 2000;343(14):998-1007.
  45. Di Iorgi N, Allegri AE, Napoli F, et al. Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases. J Clin Endocrinol Metab. 2014;99(4):1264-1272.
  46. Schreckinger M, Szerlip N, Mittal S. Diabetes insipidus following resection of pituitary tumors. Clin Neurol Neurosurg. 2013;115(2):121-126.
  47. Juul KV, Schroeder M, Rittig S, Norgaard JP. National Surveillance of Central Diabetes Insipidus (CDI) in Denmark: results from 5 years registration of 9309 prescriptions of desmopressin to 1285 CDI patients. J Clin Endocrinol Metab. 2014;99(6):2181-2187.
  48. Nemergut EC, Zuo Z, Jane JA, Jr., Laws ER, Jr. Predictors of diabetes insipidus after transsphenoidal surgery: a review of 881 patients. J Neurosurg. 2005;103(3):448-454.
  49. Kristof RA, Rother M, Neuloh G, Klingmuller D. Incidence, clinical manifestations, and course of water and electrolyte metabolism disturbances following transsphenoidal pituitary adenoma surgery: a prospective observational study. J Neurosurg. 2009;111(3):555-562.
  50. Agha A, Liew A, Finucane F, et al. Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency. Clinical endocrinology. 2004;60(6):688-693.
  51. Aimaretti G, Ambrosio MR, Di Somma C, et al. Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study. J Clin Endocrinol Metab. 2005;90(11):6085-6092.
  52. Ananthakrishnan S. Diabetes insipidus in pregnancy: etiology, evaluation, and management. Endocr Pract. 2009;15(4):377-382.
  53. Aleksandrov N, Audibert F, Bedard MJ, Mahone M, Goffinet F, Kadoch IJ. Gestational diabetes insipidus: a review of an underdiagnosed condition. J Obstet Gynaecol Can. 2010;32(3):225-231.
  54. Saborio P, Tipton GA, Chan JC. Diabetes insipidus. Pediatr Rev. 2000;21(4):122-129; quiz 129.
  55. Hadjizacharia P, Beale EO, Inaba K, Chan LS, Demetriades D. Acute diabetes insipidus in severe head injury: a prospective study. J Am Coll Surg. 2008;207(4):477-484.
  56. Timper K, Fenske W, Kuhn F, et al. Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study. J Clin Endocrinol Metab. 2015;100(6):2268-2274.
  57. Vande Walle J, Stockner M, Raes A, Norgaard JP. Desmopressin 30 years in clinical use: a safety review. Curr Drug Saf. 2007;2(3):232-238.
  58. Arima H, Oiso Y, Juul KV, Norgaard JP. Efficacy and safety of desmopressin orally disintegrating tablet in patients with central diabetes insipidus: results of a multicenter open-label dose-titration study. Endocr J. 2013;60(9):1085-1094.
  59. Kennedy PG, Mitchell DM, Hoffbrand BI. Severe hyponatraemia in hospital inpatients. Br Med J. 1978;2(6147):1251-1253.
  60. Gross P, Reimann D, Neidel J, et al. The treatment of severe hyponatremia. Kidney Int Suppl. 1998;64:S6-11.
  61. Hannon MJ, Thompson CJ. The syndrome of inappropriate antidiuretic hormone: prevalence, causes and consequences. Eur J Endocrinol. 2010;162 Suppl 1:S5-12.
  62. Ragnarsson O, Mattsson AF, Monson JP, et al. The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients. Eur J Endocrinol. 2014;171(5):571-579.
  63. Sherlock M, O’Sullivan E, Agha A, et al. Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients. Postgrad Med J. 2009;85(1002):171-175.
  64. Patterson JH. The impact of hyponatremia. Pharmacotherapy. 2011;31(5 Suppl):5S-8S.
  65. Mohan S, Gu S, Parikh A, Radhakrishnan J. Prevalence of hyponatremia and association with mortality: results from NHANES. Am J Med. 2013;126(12):1127-1137 e1121.
  66. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 Suppl 1):S1-42.
  67. Jahangiri A, Wagner J, Tran MT, et al. Factors predicting postoperative hyponatremia and efficacy of hyponatremia management strategies after more than 1000 pituitary operations. J Neurosurg. 2013;119(6):1478-1483.
  68. Callahan MA, Do HT, Caplan DW, Yoon-Flannery K. Economic impact of hyponatremia in hospitalized patients: a retrospective cohort study. Postgrad Med. 2009;121(2):186-191.
  69. Sherlock M, Reulen RC, Alonso AA, et al. ACTH deficiency, higher doses of hydrocortisone replacement, and radiotherapy are independent predictors of mortality in patients with acromegaly. J Clin Endocrinol Metab. 2009;94(11):4216-4223.
  70. Deitelzweig S, Amin A, Christian R, Friend K, Lin J, Lowe TJ. Health care utilization, costs, and readmission rates associated with hyponatremia. Hosp Pract (1995). 2013;41(1):89-95.
  71. Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120(11 Suppl 1):S1-21.
  72. Levy A. Pituitary disease: presentation, diagnosis, and management. J Neurol Neurosurg Psychiatry. 2004;75 Suppl 3:iii47-52.
  73. Agustsson TT, Baldvinsdottir T, Jonasson JG, et al. The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur J Endocrinol. 2015;173(5):655-664.
  74. 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(3):377-382.
  75. Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab. 2006;91(12):4769-4775.
  76. Burton T, Le Nestour E, Neary M, Ludlam WH. Incidence and prevalence of acromegaly in a large US health plan database. Pituitary. 2016.
  77. Mercado M, Gonzalez B, Vargas G, et al. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. J Clin Endocrinol Metab. 2014;99(12):4438-4446.
  78. Broder MS, Neary MP, Chang E, Cherepanov D, Katznelson L. Treatments, complications, and healthcare utilization associated with acromegaly: a study in two large United States databases. Pituitary. 2014;17(4):333-341.
  79. Nachtigall L, Delgado A, Swearingen B, Lee H, Zerikly R, Klibanski A. Changing patterns in diagnosis and therapy of acromegaly over two decades. J Clin Endocrinol Metab. 2008;93(6):2035-2041.
  80. Katznelson L, Laws ER, Jr., Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(11):3933-3951.
  81. Casanueva FF, Molitch ME, Schlechte JA, et al. Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas. Clin Endocrinol (Oxf). 2006;65(2):265-273.
  82. Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocr Rev. 2006;27(5):485-534.
  83. Klibanski A. Clinical practice. Prolactinomas. N Engl J Med. 2010;362(13):1219-1226.
  84. Schlechte JA. Clinical practice. Prolactinoma. N Engl J Med. 2003;349(21):2035-2041.
  85. Schlechte J, el-Khoury G, Kathol M, Walkner L. Forearm and vertebral bone mineral in treated and untreated hyperprolactinemic amenorrhea. J Clin Endocrinol Metab. 1987;64(5):1021-1026.
  86. Ciccarelli A, Daly AF, Beckers A. The epidemiology of prolactinomas. Pituitary. 2005;8(1):3-6.
  87. Sheplan Olsen LJ, Robles Irizarry L, Chao ST, et al. Radiotherapy for prolactin-secreting pituitary tumors. Pituitary. 2012;15(2):135-145.
  88. Colao A, Vitale G, Cappabianca P, et al. Outcome of cabergoline treatment in men with prolactinoma: effects of a 24-month treatment on prolactin levels, tumor mass, recovery of pituitary function, and semen analysis. J Clin Endocrinol Metab. 2004;89(4):1704-1711.
  89. Karavitaki N, Dobrescu R, Byrne JV, Grossman AB, Wass JA. Does hypopituitarism recover when macroprolactinomas are treated with cabergoline? Clin Endocrinol (Oxf). 2013;79(2):217-223.
  90. Warfield A, Finkel DM, Schatz NJ, Savino PJ, Snyder PJ. Bromocriptine treatment of prolactin-secreting pituitary adenomas may restore pituitary function. Ann Intern Med. 1984;101(6):783-785.
  91. Wang AT, Mullan RJ, Lane MA, et al. Treatment of hyperprolactinemia: a systematic review and meta-analysis. Syst Rev. 2012;1:33.
  92. Amlashi FG, Tritos NA. Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management. Endocrine. 2016.
  93. Azzalin A, Appin CL, Schniederjan MJ, et al. Comprehensive evaluation of thyrotropinomas: single-center 20-year experience. Pituitary. 2015.
  94. Jha S, Kumar S. TSH secreting pituitary adenoma. J Assoc Physicians India. 2009;57:537-539.
  95. Onnestam L, Berinder K, Burman P, et al. National incidence and prevalence of TSH-secreting pituitary adenomas in Sweden. J Clin Endocrinol Metab. 2013;98(2):626-635.
  96. Sughrue ME, Chang EF, Gabriel RA, Aghi MK, Blevins LS. Excess mortality for patients with residual disease following resection of pituitary adenomas. Pituitary. 2011;14(3):276-283.
  97. Malchiodi E, Profka E, Ferrante E, et al. Thyrotropin-secreting pituitary adenomas: outcome of pituitary surgery and irradiation. J Clin Endocrinol Metab. 2014;99(6):2069-2076.

 

Back to Top