Introduction: Non-functioning pituitary adenomas (NFPA) account for about 40% of pituitary tumors. Pituitary deficiencies are present at diagnosis in 60-80% of NFPA, and, classically, growth hormone (GH) secretion is lost first, while adrenocorticotropic hormone is expected to disappear last. The aim of this study was to evaluate the incidence of multiple or isolated pituitary deficiencies in a large series of NFPA. Materials and Methods: We retrospectively analyzed data on 218 NFPA cases (59% females, 59% with macroadenomas, average age: 50.2 ± 17 years) followed up at our center from 1990 to 2013. At diagnosis all patients had a complete evaluation of pituitary function in basal conditions and provocative tests for the hypothalamic-pituitary-adrenal axis, while tests for GH deficiency (GHD) were carried out in 38%. Results: 52.3% of patients (65.6% of macroadenomas, 33.3% of microadenomas) presented at least 1 pituitary deficiency: isolated deficiency in 29.8%, multiple deficiencies in 30% and panhypopituitarism in 9%. Isolated deficiencies were hypogonadism in 11.5% of patients (8% in micro-, 14% in macroadenomas), hypoadrenalism in 10.1% (14% in micro-, 7% in macroadenomas) and GHD in 8.3% (8.9% in micro-, 7.8% in macroadenomas). About 30% of microadenomas had at least 1 pituitary deficiency at diagnosis, independently of tumor localization within the sellar region. Conclusions: The presence of isolated hypoadrenalism suggests that the order of appearance of hypopituitarism does not always follow the one expected. Given the relatively high prevalence of isolated hypoadrenalism even in microadenomas, we suggest a full assessment of basal and dynamic pituitary function in all NFPA regardless of tumor size.

Keywords:
Non-functioning pituitary adenoma, Hypopituitarism, Hypoadrenalism
1.
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;55:735-740.
2.
Ehrnborq C, Hakkaart-Van Roijen L, Jonsson B, Rutten FF, Bengtsson BA, Rosen T: Cost of illness in adult patients with hypopituitarism. Pharmacoeconomics 2000;17:621-628.
3.
Peters JP, German WJ, Man EB, Welt LG: Functions of gonads, thyroid and adrenals in hypopituitarism. Metabolism 1954;3:118-137.
4.
Rabkin MT, Frantz AG: Hypopituitarism: a study of growth hormone and other endocrine functions. Ann Intern Med 1966;64:1197-1207.
5.
Comtois R, Beauregard H, Somma M, Serri O, Aris-Jilwan N, Hardy J: The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas. Cancer 1991;68:860-866.
6.
Tominaga A, Uozumi T, Arita K, Kurisu K, Yano T, Hirohata T: Anterior pituitary function in patients with nonfunctioning pituitary adenoma: results of longitudinal follow-up. Endocr J 1995;42:421-427.
7.
Nomikos P, Ladar C, Fahlbusch R, Buchfelder M: Impact of primary surgery on pituitary function in patients with non-functioning pituitary adenomas - a study on 721 patients. Acta Neurochir (Wien) 2004;146:27-35.
8.
Dekkers OM, Pereira AM, Roelfsema F, Voormolen JH, Neelis KJ, Schroijen MA, Smit JW, Romijn JA: Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma. J Clin Endocrinol Metab 2006;91:1796-1801.
9.
Fatemi N, Dusick JR, Mattozo C, McArthur DL, Cohan P, Boscardin J, Wang C, Swerdloff RS, Kelly DF: Pituitary hormonal loss and recovery after transsphenoidal adenoma removal. Neurosurgery 2008;63:709-718.
10.
Buurman H, Saeger W: Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data. Eur J Endocrinol 2006;154:753-758.
11.
Daly AF, Rixhon M, Adam C, et al: High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 2006;91:4769-4775.
12.
Davis JR, Farrell WE, Clayton RN: Pituitary tumours. Reproduction 2001;121:363-371.
13.
Ferrante E, Ferraroni M, Castrignanò T, Menicatti L, Anagni M, Reimondo G, Del Monte P, Bernasconi D, Loli P, Faustini-Fustini M, Borretta G, Terzolo M, Losa M, Morabito A, Spada A, Beck-Peccoz P, Lania AG: Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. Eur J Endocrinol 2006;155:823-829.
14.
Drange MR, Fram NR, Herman-Bonert V, Melmed S: Pituitary tumor registry: a novel clinical resource. J Clin Endocrinol Metab 2000;85:168-174.
15.
Arafah BM: Medical management of hypopituitarism in patients with pituitary adenomas. Pituitary 2002;5:109-117.
16.
Jones SL, Trainer PJ, Perry L, Wass JA, Besser GM, Grossman A: An audit of the insulin tolerance test in adult subjects in an acute investigation unit over one year. Clin Endocrinol (Oxf) 1994;41:123-128.
17.
Charmandari E, Nicolaides NC, Chrousos GP: Adrenal insufficiency. Lancet 2014;383:2152-2167.
18.
Kazlauskaite R, Evans AT, Villabona CV, Abdu TA, Ambrosi B, Atkinson AB, Choi CH, Clayton RN, Courtney CH, Gonc EN, Maghnie M, Rose SR, Soule SG, Tordjman K: Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 2008;93:4245-4253.
19.
Ho KK: Consensus guidelines for the diagnosis and treatment of adults with GH deficiency. II. A statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol 2007;157:695-700.
20.
Corneli G, Di Somma C, Prodam F, Bellone J, Bellone S, Gasco V, Baldelli R, Rovere S, Schneider HJ, Gargantini L, Gastaldi R, Ghizzoni L, Valle D, Salerno M, Colao A, Bona G, Ghigo E, Maghnie M, Aimaretti G: Cut-off limits of the GH response to GHRH plus arginine test and IGF-I levels for the diagnosis of GH deficiency in late adolescents and young adults. Eur J Endocrinol 2007;157:701-708.
21.
Hartman ML, Crowe BJ, Biller BM, Ho KK, Clemmons DR, Chipman JJ; HyposCCS Advisory Board; US HypoCCS Study Group: Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency? J Clin Endocrinol Metab 2002;87:477-485.
22.
Alexopoulou O, Beguin C, De Nayer P, Maiter D: Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients. Eur J Endocrinol 2004;150:1-8.
23.
Toogood AA, Stewart PM: Hypopituitarism: clinical features, diagnosis, and management. Endocrinol Metab Clin North Am 2008;37:235-261.
24.
Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM: Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010;95:2536-2559.
25.
Karavitaki N, Thanabalasingham G, Shore HC, Trifanescu R, Ansorge O, Meston N, Turner HE, Wass JA: 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;65:524-529.
26.
Sala E, Ferrante E, Locatelli M, Rampini P, Mantovani G, Giavoli C, Filopanti M, Verrua E, Malchiodi E, Carrabba G, Arosio M, Beck-Peccoz P, Spada A, Lania AG: Diagnostic features and outcome of surgical therapy of acromegalic patients: experience of the last three decades. Hormones (Athens) 2014;13:95-103.
27.
Ferrante E, Morelli V, Giavoli C, Mantovani G, Verrua E, Sala E, Malchiodi E, Bergamaschi S, Profka E, Cairoli E, Palmieri S, Chiodini I, Lania AG, Spada A, Beck Peccoz P: Is the 250 μg ACTH test a useful tool for the diagnosis of central hypoadrenalism in adult patients with pituitary disorders? Hormones (Athens) 2012;11:428-435.
28.
Ambrosi B, Barbetta L, Re T, Passini E, Faglia G: The one microgram adrenocorticotropin test in the assessment of hypothalamic-pituitary-adrenal function. Eur J Endocrinol 1998;139:575-579.
29.
Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML: Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1587-1609.
30.
Yuen KC, Cook DM, Sahasranam P, Patel P, Ghods DE, Shahinian HK, Friedman TC: Prevalence of GH and other anterior pituitary hormone deficiencies in adults with nonsecreting pituitary microadenomas and normal serum IGF-1 levels. Clin Endocrinol (Oxf) 2008;69:292-298.
31.
Crichton M, Christy NP, Damon A: Host factors in ‘chromophobe' adenoma of the anterior pituitary: a retrospective study of 464 patients. Metabolism 1981;30:248-267.
32.
Losa M, Mortini P, Barzaghi R, Ribotto P, Terreni MR, Marzoli SB, Pieralli S, Giovanelli M: Early results of surgery in patients with nonfunctioning pituitary adenoma and analysis of the risk of tumor recurrence. J Neurosurg 2008;108:525-532.
33.
Heaney AP, Melmed S: Molecular targets in pituitary tumors. Nat Rev Cancer 2004;4:285-295.
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2015
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