Horm Metab Res 2013; 45(01): 54-61
DOI: 10.1055/s-0032-1323702
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Pituitary Function in Patients with Hereditary Haemochromatosis

P. M. Uitz
1   Division of Endocrinology & Diabetology, Faculty of Medicine and University Hospital, Philipp’s University, Marburg, Germany
,
S. Hartleb
1   Division of Endocrinology & Diabetology, Faculty of Medicine and University Hospital, Philipp’s University, Marburg, Germany
,
S. Schaefer
1   Division of Endocrinology & Diabetology, Faculty of Medicine and University Hospital, Philipp’s University, Marburg, Germany
,
N. Al-Fakhri
2   Center for In Vitro Diagnostics – Endocrinology, Faculty of Medicine and University Hospital, Philipp’s University, Marburg, Germany
3   Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Faculty of Medicine and University Hospital, Philipp’s University, Marburg, Germany
,
P. H. Kann
1   Division of Endocrinology & Diabetology, Faculty of Medicine and University Hospital, Philipp’s University, Marburg, Germany
2   Center for In Vitro Diagnostics – Endocrinology, Faculty of Medicine and University Hospital, Philipp’s University, Marburg, Germany
› Author Affiliations
Further Information

Publication History

received 23 March 2012

accepted 26 July 2012

Publication Date:
02 October 2012 (online)

Abstract

Haemochromatosis may impair the function of endocrine organs, amongst others the pituitary gland. It was the aim of this study to determine pituitary function in adult patients with genetically defined hereditary haemochromatosis in a prospective diagnostic study using a standardised stimulation test. Therefore, 22 patients (7 females, 15 males; age at diagnosis of haemochromatosis 48.1±7.9 years; age at study inclusion 50.7±7.7 years) with genetically defined hereditary haemochromatosis were investigated by a combined pituitary stimulation test (CRH, GHRH/arginine, GnRH, TRH). In 11 patients (50% of the study population; 2 females, 9 males), pituitary insufficiencies were detected [isolated corticotrophic insufficiency (peak cortisol < 181.25 μg/l/500 nmol/l) n=10 (2 females, 8 males); combined corticotrophic and borderline gonadotrophic insufficiency (basal testosterone 2.4–3.0 μg/l without basal LH-elevation) in 1 male]. Somatotrophic pituitary insufficiencies were not found. IFG-1 concentrations below –2 standard deviations in 7 patients (32%) may be attributed to impaired hepatic IGF-1 synthesis. Hypopituitarism, particularly corticotrophic insufficiency, seems to be prevalent in a considerable number of middle-aged patients with hereditary haemochromatosis. Despite normal somatotrophic function, low IGF-1 serum concentrations may be found in a subgroup of haemochromatosis patients.

 
  • References

  • 1 Franchini M. Hereditary Iron Overload: Update on pathophysiology, diagnosis, and treatment. Am J Hematol 2006; 81: 202-209
  • 2 Edwards CQ, Griffen LM, Goldgar D, Drummond C, Skolnick MH, Kushner JP. Prevalence of hemochromatosis among 11 065 presumably healthy blood donors. N Engl J Med 1998; 318: 1355-1362
  • 3 Edwards CQ, Kushner JP. Screening for hemochromatosis. N Engl J Med 1993; 328: 1616-1620
  • 4 Pippard MJ. Detection of iron overload. Lancet 1997; 349: 73-74
  • 5 Niederau C, Niederau CM, Lange S, Littauer A, Abdel-Jalil N, Maurer M, Haussinger G, Strohmeyer G. Screening for hemochromatosis and iron deficiency in employees and primary care patients in Western Germany. Ann Intern Med 1998; 128: 337-345
  • 6 Merryweather-Clarke AT, Pointon JJ, Jouanolle AM, Rochette J, Robson KIH. Geography of HFE C282Y and H63D mutations. Genet Test 2000; 4: 183-198
  • 7 Hanson EH, Imperatore G, Burke W. HFE gene and hemochromatosis: a huge review. Am J Epidemiol 2001; 154: 193-206
  • 8 Olynyk JK, Cullen DJ, Aquilia S, Rossi E, Summerville L, Powell LW. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999; 341: 718-724
  • 9 Bacon BR, Olynyk JK, Brunt EM, Britton RS, Wolff RK. HFE genotype in patients with hemochromatosis and other liver diseases. Ann Intern Med 1999; 130: 953-962
  • 10 Gochee PA, Powell LW, Cullen DJ, Du Sart D, Rossi E, Olynyk JK. A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation. Gastroenterology 2002; 122: 646-651
  • 11 Edwards CQ, Skolnick MH, Dadone MM, Kushner JP. Iron overload in hereditary spherocytosis: association with HLA-linked hemochromatosis. Am J Hematol 1982; 13: 101-109
  • 12 Niederau C, Strohmeyer G, Stremmel W. Epidemiology, clinical spectrum and prognosis of hemochromatosis. Adv Exp Med Biol 1994; 356: 293-302
  • 13 McDonnell SM, Preston BL, Jewell SA, Barton JC, Edwards CQ, Adams PC, Yip R. A survey of 2,851 patients with hemochromatosis: symptoms and response to treatment. Am J Med 1999; 106: 619-624
  • 14 McDermott JH, Walsh CH. Extensive clinical experience. Hypogonadism in hereditary hemochromatosis. J Clin Endocrinol Metab 2005; 90: 2451-2455
  • 15 Kelly TM, Edwards CQ, Meikle AW, Kushner JP. Hypogonadism in hemochromatosis: reversal with iron depletion. Ann Intern Med 1984; 101: 629-632
  • 16 Tweed MJ, Roland JM. Haemochromatosis as an endocrine cause of subfertility. Brit Med J 1998; 316: 915-916
  • 17 Gama R, Smith MJ, Wright J, Marks V. Hypopituitarism in primary haemochromatosis; recovery after iron depletion. Postgrad Med J 1995; 71: 297-298
  • 18 Wahid S, Ball S. Hereditary iron overload: Update on pathophysiology, diagnosis, and treatment. Lancet 2001; 357: 115
  • 19 Paris I, Hermans M, Buysschaert M. Endocrine complications of genetic hemochromatosis. Acta Clin Belg 1999; 54: 334-345
  • 20 Walton C, Kelly WF, Laing I, Bu’lock DE. Endocrine abnormalities in idiopathic haemochromatosis. Q J Med 1983; 52: 99-110
  • 21 Charbonnel B, Chupin M, Le Grand A, Guillon J. Pituitary function in idiopathic haemochromatosis: hormonal study in 36 male patients. Acta Endocrinol (Copenh) 1981; 98: 178-183
  • 22 Pedersen-Bjergaard U, Thorsteinsson B, Kirkegaard BC. Pituitary function in hemochromatosis. Ugeskr Læger 1996; 158: 1818-1822
  • 23 Kreitschmann-Andermahr I, Hoff C, Saller B, Niggemeier S, Pruemper S, Huetter BO, Rohde V, Gressner A, Matern S, Gilsbach JM. Prevalence of pituitary deficiency in patients after aneurysmal subarachnoid hemorrhage. J Clin Endocrinol Metab 2004; 89: 4986-4992
  • 24 Schaefer S, Boegershausen N, Meyer S, Ivan D, Schepelmann K, Kann PH. Hypothalamic–pituitary insufficiency following infectious diseases of the central nervous system. Eur J Endocrinol 2008; 158: 3-9
  • 25 Utzschneider KM, Kowdley KV. Hereditary hemochromatosis and diabetes mellitus: Implications for clinical practice. Nat Rev Endocrinol 2010; 6: 26-33
  • 26 Niederau C. Diabetes mellitus bei Hämochromatose. Z Gastroenterol 1999; (Suppl. 01) 22-32
  • 27 Kleinbau J, Shamoon H. Impaired counterregulation of hypoglycemia in insulin-dependent diabetes mellitus. Diabetes 1983; 32: 493-498
  • 28 Bolli GB, Dimitriadis GD, Pehling GB, Baker BA, Haymond MW, Cryer PE, Gerich JE. Abnormal glucose counterregulation after subcutaneous insulin in insulin-dependent diabetes mellitus. N Engl J Med 1984; 310: 1706-1711
  • 29 Davis MR, Shamoon H. Counterregulatory adaptation to recurrent hypoglycemia in normal humans. J Clin Endocrinol Metab 1991; 73: 995-1001
  • 30 Schneider S, Beyer J, Sarnighausen HE, Burchert D, Kann P, Küstner E, Kunt T. Vergleich des Hypoglykämieempfindens und der hormonellen Gegenregulation während einer kontrollierten Hypoglykämie. Ein Beitrag zur Diagnostik des Hypoglykämie-Unawareness-Syndroms bei Typ-1-Diabetikern. Dtsch Med Wochenschr 2000; 125: 177-181
  • 31 Israelian Z, Szoke E, Woerle J, Bokhari S, Schorr M, Schwenke DC, Cryer PE, Gerich JE, Meyer C. Multiple defects in counterregulation of hypoglycemia in modestly advanced type 2 diabetes mellitus. Metabolism 2006; 55: 593-598
  • 32 Ho KKY. 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
  • 33 Schaefer S, Vogt T, Nowak T, Kann PH. Pituitary function and the somatotrophic system in patients with idiopathic Parkinson’s disease under chronic dopaminergic therapy. J Neuroendocrinol 2008; 20: 104-109
  • 34 Maghnie M, Uga E, Temporini F, Di Iorgi N, Secco A, Tinelli C, Papalia A, Casini MR, Loche S. Evaluation of adrenal function in patients with growth hormone deficiency and hypothalamic-pituitary disorders: comparison between insulin-induced hypoglycemia, low-dose ACTH, standard ACTH and CRH stimulation tests. Eur J Endocrinol 2005; 152: 735-741
  • 35 Clark P, Britton LJ, Powell LW. The diagnosis and management of hereditary haemochromatosis. Clin Biochem Rev 2010; 31: 3-8
  • 36 Ayonrinde OT, Milward EA, Chua AC, Trinder D, Olynyk JK. Clinical perspectives on hereditary hemochromatosis. Crit Rev Cl Lab Sci 2008; 45: 451-484
  • 37 Elmlinger MW, Kühnel W, Weber MM, Ranke MB. Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3). Clin Chem Lab Med 2004; 42: 654-664
  • 38 Nieschlag E, Swerdloff R, Behre HM, Gooren LJ, Kaufmann JM, Legros JJ, Lunenfeld B, Morley JE, Schulman C, Wang C, Weidner W, Wu FC. Investigation, treatment and monitoring of late-onset hypogonadism in males. ISA, ISSAM, and EAU recommendations. Eur J Urol 2005; 48: 1-4
  • 39 Lehnert H. Rationelle Diagnostik und Therapie in Endokrinologie, Diabetologie und Stoffwechsel. 3rd ed. Stuttgart: Georg Thieme Verlag; 2009: 505-506
  • 40 Petersenn S, Quabbe H-J, Schöfl C, Stalla GK, von Werder K, Buchfelder M. The rational use of pituitary stimulation tests. Dtsch Arztebl Int 2010; 107: 437-443
  • 41 Impallomeni M, Yeo T, Rudd A, Carr D, Aber V. Investigation of anterior pituitary function in elderly in-patients over the age of 75. Q J Med 1987; 63: 505-515
  • 42 Spencer CA, Schwarzbein D, Guttler RB, LoPresti JS, Nicoloff JT. Thyrotropin (TSH)-releasing hormone stimulation test responses employing third and fourth generation TSH assays. J Clin Endocrinol Metab 1993; 76: 494-498
  • 43 Schmidt IL, Lahner H, Mann K, Petersenn S. Diagnosis of adrenal insufficiency: Evaluation of the corticotropin-releasing hormone test and basal serum cortisol in comparison to the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease. J Clin Endocrinol Metab 2003; 88: 4193-4198
  • 44 Agha A, Rogers B, Sherlock M, O’Kelly P, Tormey W, Phillipps J, Thomson CJ. Anterior pituitary dysfunction in survivors of traumatic brain injury. J Clin Endocrinol Metab 2004; 89: 4929-4936