, Volume 8, Issue 3–4, pp 183–191 | Cite as

Diagnosis and Treatment of Hypopituitarism: An Update

  • M. O. van Aken
  • S. W. J. Lamberts


Diagnosis and treatment of patients with hypopituitarism needs careful clinical evaluation and individual optimization. Symptoms of hypopituitarism are variable, often insidious in onset and dependent on the degree of hormone deficiency. Diagnosis of hypopituitarism can be straightforward by measuring reduced basal hormone levels. Frequently, dynamic stimulation tests are indicated in equivocal basal hormone levels or to diagnose partial hormone deficiencies. Knowledge of the use and limitations of these dynamic tests is mandatory for proper interpretation.

Hormone replacement therapy should be individualized, taking into account possible interactions. Persisting symptoms and reduced quality of life are frequently reported, explained by, at least in part, intrinsic imperfections of hormone replacement strategies in mimicking normal hormone secretion.

In the present overview, the principles of diagnosis and treatment of hypopituitarism are discussed.

Key Words

Hypopituitarism pituitary diagnosis hormone replacement therapy quality of life 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lamberts SW, de Herder WW, van der Lely AJ. Pituitary insufficiency. Lancet 1998;352(9122):127–134.CrossRefPubMedGoogle Scholar
  2. 2.
    Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003;361(9372):1881–1893.CrossRefPubMedGoogle Scholar
  3. 3.
    Streeten DH. What test for hypothalamic-pituitary-adrenocortical insufficiency? Lancet 1999;354(9174):179–180.CrossRefPubMedGoogle Scholar
  4. 4.
    Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med 2003;139(3):194–204.PubMedGoogle Scholar
  5. 5.
    Tuchelt H, Dekker K, Bahr V, Oelkers W. Dose-response relationship between plasma ACTH and serum cortisol in the insulin-hypoglycaemia test in 25 healthy subjects and 109 patients with pituitary disease. Clin Endocrinol (Oxf) 2000;53(3):301–307.CrossRefGoogle Scholar
  6. 6.
    Stewart PM, Clark PM, Sheppard MC. Comparison of the short ACTH stimulation test with the insulin tolerance/glucagon test. Clin Endocrinol (Oxf) 1998;48(1):124–126.CrossRefGoogle Scholar
  7. 7.
    Binder G, Bosk A, Gass M, Ranke MB, Heidemann PH. Insulin tolerance test causes hypokalaemia and can provoke cardiac arrhythmias. Horm Res 2004;62(2):84–87.CrossRefPubMedGoogle Scholar
  8. 8.
    Spiger M, Jubiz W, Meikle AW, West CD, Tylor FH. Single-dose metyrapone test: review of a four-year experience. Arch Intern Med 1975;135(5):698–700.CrossRefPubMedGoogle Scholar
  9. 9.
    Berneis K, Staub JJ, Gessler A, Meier C, Girard J, Muller B. Combined stimulation of adrenocorticotropin and compound-S by single dose metyrapone test as an outpatient procedure to assess hypothalamic-pituitary-adrenal function. J Clin Endocrinol Metab 2002;87(12):5470–5475.CrossRefPubMedGoogle Scholar
  10. 10.
    Esteban NV, Loughlin T, Yergey AL, et al. Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. J Clin Endocrinol Metab 1991;72(1):39–45.PubMedGoogle Scholar
  11. 11.
    Peacey SR, Guo CY, Robinson AM, et al. Glucocorticoid replacement therapy: are patients over treated and does it matter? Clin Endocrinol (Oxf) 1997;46(3):255–261.CrossRefGoogle Scholar
  12. 12.
    Suliman AM, Freaney R, Smith TP, McBrinn Y, Murray B, McKenna TJ. The impact of different glucocorticoid replacement schedules on bone turnover and insulin sensitivity in patients with adrenal insufficiency. Clin Endocrinol (Oxf) 2003;59(3):380–387.CrossRefGoogle Scholar
  13. 13.
    Agha A, Liew A, Finucane F, et al. Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency. Clin Endocrinol (Oxf) 2004;60(6):688–693.CrossRefGoogle Scholar
  14. 14.
    Wong V, Yan T, Donald A, McLean M. Saliva and bloodspot cortisol: novel sampling methods to assess hydrocortisone replacement therapy in hypoadrenal patients. Clin Endocrinol (Oxf) 2004;61(1):131–137.CrossRefGoogle Scholar
  15. 15.
    Charmandari E, Johnston A, Brook CG, Hindmarsh PC. Bioavailability of oral hydrocortisone in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Endocrinol 2001;169(1):65–70.CrossRefPubMedGoogle Scholar
  16. 16.
    Blomgren J, Ekman B, Andersson PO, Arnqvist HJ. Non-physiological levels of circulating cortisol in growth hormone-treated hypopituitary adults after conventional cortisone substitution. Scand J Clin Lab Invest 2004;64(2):132–139.PubMedGoogle Scholar
  17. 17.
    Nasrallah MP, Arafah BM. The value of dehydroepiandrosterone sulfate measurements in the assessment of adrenal function. J Clin Endocrinol Metab 2003;88(11):5293–5298.CrossRefPubMedGoogle Scholar
  18. 18.
    Aimaretti G, Baffoni C, Ambrosio MR, et al. DHEA-S levels in hypopituitaric patients with severe GH deficiency are strongly reduced across lifespan. Comparison with IGF-I levels before and during rhGH replacement. J Endocrinol Invest 2000;23(1):5–11.PubMedGoogle Scholar
  19. 19.
    Arlt W, Callies F, van Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med 1999;341(14):1013–1020.CrossRefPubMedGoogle Scholar
  20. 20.
    Hunt PJ, Gurnell EM, Huppert FA, et al. Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial. J Clin Endocrinol Metab 2000;85(12):4650–4656.CrossRefPubMedGoogle Scholar
  21. 21.
    Johannsson G, Burman P, Wiren L, et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. J Clin Endocrinol Metab 2002;87(5):2046–2052.CrossRefPubMedGoogle Scholar
  22. 22.
    Lovas K, Gebre-Medhin G, Trovik TS, et al. Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial. J Clin Endocrinol Metab 2003;88(3):1112–1118.CrossRefPubMedGoogle Scholar
  23. 23.
    van Thiel SW, Romijn JA, Pereira AM, et al. Effects of DHEA, superimposed on growth hormone substitution, on quality of life and IGF-I in patients with secondary adrenal insufficiency: a randomised, placebo controlled, crossover trial. J Clin Endocrinol Metab 2005.Google Scholar
  24. 24.
    Allahabadia A, Weetman AP. Dynamic thyroid stimulating hormone tests: do they still have a role? J Endocrinol Invest 2003;26(7 Suppl):31–38.PubMedGoogle Scholar
  25. 25.
    Mehta A, Hindmarsh PC, Stanhope RG, Brain CE, Preece MA, Dattani MT. Is the thyrotropin-releasing hormone test necessary in the diagnosis of central hypothyroidism in children. J Clin Endocrinol Metab 2003;88(12):5696–5703.CrossRefPubMedGoogle Scholar
  26. 26.
    Ferretti E, Persani L, Jaffrain-Rea ML, Giambona S, Tamburrano G, Beck-Peccoz P. Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism. J Clin Endocrinol Metab 1999;84(3):924–929.CrossRefPubMedGoogle Scholar
  27. 27.
    Sawka AM, Gerstein HC, Marriott MJ, MacQueen GM, Joffe RT. Does a combination regimen of thyroxine (T4) and 3,5,3′-triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism? Results of a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 2003;88(10):4551–4555.CrossRefPubMedGoogle Scholar
  28. 28.
    Walsh JP, Shiels L, Lim EM, et al. Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism. J Clin Endocrinol Metab 2003;88(10):4543–4550.CrossRefPubMedGoogle Scholar
  29. 29.
    Roberts CG, Ladenson PW. Hypothyroidism. Lancet 2004;363(9411):793–803.CrossRefPubMedGoogle Scholar
  30. 30.
    Zitzmann M, Nieschlag E. Hormone substitution in male hypogonadism. Mol Cell Endocrinol 2000;161(1–2):73–88.PubMedGoogle Scholar
  31. 31.
    Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 2004;350(5):482–492.CrossRefPubMedGoogle Scholar
  32. 32.
    Toogood AA, Taylor NF, Shalet SM, Monson JP. Modulation of cortisol metabolism by low-dose growth hormone replacement in elderly hypopituitary patients. J Clin Endocrinol Metab 2000;85(4):1727–1730.CrossRefPubMedGoogle Scholar
  33. 33.
    Hartman ML, Crowe BJ, Biller BM, Ho KK, Clemmons DR, Chipman JJ. Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency? J Clin Endocrinol Metab 2002;87(2):477–485.CrossRefPubMedGoogle Scholar
  34. 34.
    Hoffman DM, O’Sullivan AJ, Baxter RC, Ho KK. Diagnosis of growth-hormone deficiency in adults. Lancet 1994;343(8905):1064–1068.CrossRefPubMedGoogle Scholar
  35. 35.
    Aimaretti G, Corneli G, Razzore P, et al. Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults. J Clin Endocrinol Metab 1998;83(5):1615–1618.CrossRefPubMedGoogle Scholar
  36. 36.
    Salameh Y, Shoufani A. Full-thickness skin necrosis after arginine extravasation–a case report and review of literature. J Pediatr Surg 2004;39(4):e9–11.CrossRefPubMedGoogle Scholar
  37. 37.
    Popovic V, Leal A, Micic D, et al. GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adults. Lancet 2000;356(9236):1137–1142.CrossRefPubMedGoogle Scholar
  38. 38.
    Qu XD, Gaw GI, Al Sayed MY, et al. Influence of body mass index and gender on growth hormone (GH) responses to GH-releasing hormone plus arginine and insulin tolerance tests. J Clin Endocrinol Metab 2005;90(3):1563–1569.PubMedGoogle Scholar
  39. 39.
    Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency. J Clin Endocrinol Metab 1998;83(2):379–381.Google Scholar
  40. 40.
    Monson JP. Biochemical markers of individual response to growth hormone replacement in adults. Horm Res 2001;55(Suppl 2):49–54.PubMedGoogle Scholar
  41. 41.
    Drake WM, Howell SJ, Monson JP, Shalet SM. Optimizing gh therapy in adults and children. Endocr Rev 2001;22(4):425–450.CrossRefPubMedGoogle Scholar
  42. 42.
    Drake WM, Coyte D, Camacho-Hubner C, et al. Optimizing growth hormone replacement therapy by dose titration in hypopituitary adults. J Clin Endocrinol Metab 1998;83(11):3913–3919.CrossRefPubMedGoogle Scholar
  43. 43.
    Drake WM, Coyte D, Camacho-Hubner C, et al. Optimizing growth hormone replacement therapy by dose titration in hypopituitary adults. J Clin Endocrinol Metab 1998;83(11):3913–3919.CrossRefPubMedGoogle Scholar
  44. 44.
    Cook DM, Biller BM, Vance ML, et al. The pharmacokinetic and pharmacodynamic characteristics of a long-acting growth hormone (GH) preparation (nutropin depot) in GH-deficient adults. J Clin Endocrinol Metab 2002;87(10):4508–4514.CrossRefPubMedGoogle Scholar
  45. 45.
    Jostel A, Mukherjee A, Alenfall J, Smethurst L, Shalet SM. A new sustained-release preparation of human growth hormone and its pharmacokinetic, pharmacodynamic and safety profile. Clin Endocrinol (Oxf) 2005;62(5):623–627.CrossRefGoogle Scholar
  46. 46.
    Rietveld I, Janssen JA, Hofman A, Pols HA, van Duijn CM, Lamberts SW. A polymorphism in the IGF-I gene influences the age-related decline in circulating total IGF-I levels. Eur J Endocrinol 2003;148(2):171–175.CrossRefPubMedGoogle Scholar
  47. 47.
    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.CrossRefPubMedGoogle Scholar
  48. 48.
    Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med 2001;344(23):1743–1749.CrossRefPubMedGoogle Scholar
  49. 49.
    Rodriguez-Arnao J, Perry L, Besser GM, Ross RJ. Growth hormone treatment in hypopituitary GH deficient adults reduces circulating cortisol levels during hydrocortisone replacement therapy. Clin Endocrinol (Oxf) 1996;45(1):33–37.Google Scholar
  50. 50.
    Swords FM, Carroll PV, Kisalu J, Wood PJ, Taylor NF, Monson JP. The effects of growth hormone deficiency and replacement on glucocorticoid exposure in hypopituitary patients on cortisone acetate and hydrocortisone replacement. Clin Endocrinol (Oxf) 2003;59(5):613–620.CrossRefGoogle Scholar
  51. 51.
    Binnerts A, Swart GR, Wilson JH, et al. The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition. Clin Endocrinol (Oxf) 1992;37(1):79–87.Google Scholar
  52. 52.
    Allolio B, Hoffmann J, Linton EA, Winkelmann W, Kusche M, Schulte HM. Diurnal salivary cortisol patterns during pregnancy and after delivery: relationship to plasma corticotrophin-releasing-hormone. Clin Endocrinol (Oxf) 1990;33(2):279–289.Google Scholar
  53. 53.
    Adams LA, Feldstein A, Lindor KD, Angulo P. Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction. Hepatology 2004;39(4):909–914.CrossRefPubMedGoogle Scholar
  54. 54.
    Mersebach H, Klose M, Svendsen OL, Astrup A, Feldt-Rasmussen U. Combined dietary and pharmacological weight management in obese hypopituitary patients. Obes Res 2004;12(11):1835–1843.PubMedGoogle Scholar
  55. 55.
    Sibal L, Ugwu P, Kendall-Taylor P, et al. Medical therapy of macroprolactinomas in males: I. Prevalence of hypopituitarism at diagnosis. II. Proportion of cases exhibiting recovery of pituitary function. Pituitary 2002;5(4):243–246.CrossRefPubMedGoogle Scholar
  56. 56.
    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.CrossRefPubMedGoogle Scholar
  57. 57.
    Arafah BM. Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 1986;62(6):1173–1179.PubMedGoogle Scholar
  58. 58.
    Arafah BM, Prunty D, Ybarra J, Hlavin ML, Selman WR. The dominant role of increased intrasellar pressure in the pathogenesis of hypopituitarism, hyperprolactinemia, and headaches in patients with pituitary adenomas. J Clin Endocrinol Metab 2000;85(5):1789–1793.CrossRefPubMedGoogle Scholar
  59. 59.
    Clayton PE, Cuneo RC, Juul A, Monson JP, Shalet SM, Tauber M. Consensus statement on the management of the GH-treated adolescent in the transition to adult care. Eur J Endocrinol 2005;152(2):165–170.CrossRefPubMedGoogle Scholar
  60. 60.
    Gleeson HK, Gattamaneni HR, Smethurst L, Brennan BM, Shalet SM. Reassessment of growth hormone status is required at final height in children treated with growth hormone replacement after radiation therapy. J Clin Endocrinol Metab 2004;89(2):662–666.CrossRefPubMedGoogle Scholar
  61. 61.
    Savage MO, Drake WM, Carroll PV, Monson JP. Transitional care of GH deficiency: when to stop GH therapy. Eur J Endocrinol 2004;151(Suppl 1):S61–S65.PubMedGoogle Scholar
  62. 62.
    Burman P, Deijen JB. Quality of life and cognitive function in patients with pituitary insufficiency. Psychother Psychosom 1998;67(3):154–167.CrossRefPubMedGoogle Scholar
  63. 63.
    Johnson MD, Woodburn CJ, Vance ML. Quality of life in patients with a pituitary adenoma. Pituitary 2003;6(2):81–87.CrossRefPubMedGoogle Scholar
  64. 64.
    Romijn JA, Smit JW, Lamberts SW. Intrinsic imperfections of endocrine replacement therapy. Eur J Endocrinol 2003;149(2):91–97.CrossRefPubMedGoogle Scholar
  65. 65.
    Malik IA, Foy P, Wallymahmed M, Wilding JP, MacFarlane IA. Assessment of quality of life in adults receiving long-term growth hormone replacement compared to control subjects. Clin Endocrinol (Oxf) 2003;59(1):75–81.CrossRefGoogle Scholar
  66. 66.
    Sanmarti A, Lucas A, Hawkins F, Webb SM, Ulied A. Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Collaborative ODA (Observational GH Deficiency in Adults) Group. Eur J Endocrinol 1999;141(5):481–489.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Erasmus Medical CentreDepartment of Internal MedicineCA, RotterdamThe Netherlands

Personalised recommendations