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Published in: European Journal of Clinical Microbiology & Infectious Diseases 6/2010

01-06-2010 | Article

Hormonal deficiencies during and after Puumala hantavirus infection

Authors: S. Mäkelä, P. Jaatinen, M. Miettinen, J. Salmi, I. Ala-Houhala, H. Huhtala, M. Hurme, I. Pörsti, A. Vaheri, J. Mustonen

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 6/2010

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Abstract

Previous reports have described panhypopituitarism associated with severe cases of hemorrhagic fever with renal syndrome (HFRS), but the prevalence of hormonal deficiencies after nephropathia epidemica (NE), a milder form of HFRS, has not been studied. This study was conducted in order to determine the prevalence of hormonal defects in patients with acute NE and during long-term follow-up. Fifty-four patients with serologically confirmed acute NE were examined by serum hormonal measurements during the acute NE, after 3 months, and after 1 to 10 (median 5) years. Thirty out of 54 (56%) patients had abnormalities of the gonadal and/or thyroid axis during the acute NE. After a median follow-up of 5 years, 9 (17%) patients were diagnosed with a chronic, overt hormonal deficit: hypopituitarism was found in five patients and primary hypothyroidism in five patients. In addition, chronic subclinical testicular failure was found in five men. High creatinine levels and inflammatory markers during NE were associated with the acute central hormone deficiencies, but not with the chronic deficiencies. Hormonal defects are common during acute NE and, surprisingly, many patients develop chronic hormonal deficiencies after NE. The occurrence of long-term hormonal defects cannot be predicted by the severity of acute NE.
Literature
1.
go back to reference Vapalahti O, Mustonen J, Lundkvist Å, Henttonen H, Plyusnin A, Vaheri A (2003) Hantavirus infections in Europe. Lancet Infect Dis 3(10):653–661CrossRefPubMed Vapalahti O, Mustonen J, Lundkvist Å, Henttonen H, Plyusnin A, Vaheri A (2003) Hantavirus infections in Europe. Lancet Infect Dis 3(10):653–661CrossRefPubMed
2.
go back to reference Lähdevirta J (1971) Nephropathia epidemica in Finland. A clinical histological and epidemiological study. Ann Clin Res 3:1–54PubMed Lähdevirta J (1971) Nephropathia epidemica in Finland. A clinical histological and epidemiological study. Ann Clin Res 3:1–54PubMed
3.
go back to reference Mustonen J, Brummer-Korvenkontio M, Hedman K, Pasternack A, Pietilä K, Vaheri A (1994) Nephropathia epidemica in Finland: a retrospective study of 126 cases. Scand J Infect Dis 26(1):7–13CrossRefPubMed Mustonen J, Brummer-Korvenkontio M, Hedman K, Pasternack A, Pietilä K, Vaheri A (1994) Nephropathia epidemica in Finland: a retrospective study of 126 cases. Scand J Infect Dis 26(1):7–13CrossRefPubMed
4.
go back to reference Settergren B, Juto P, Trollfors B, Wadell G, Norrby SR (1989) Clinical characteristics of nephropathia epidemica in Sweden: prospective study of 74 cases. Rev Infect Dis 11(6):921–927PubMed Settergren B, Juto P, Trollfors B, Wadell G, Norrby SR (1989) Clinical characteristics of nephropathia epidemica in Sweden: prospective study of 74 cases. Rev Infect Dis 11(6):921–927PubMed
5.
go back to reference Mustonen J, Partanen J, Kanerva M, Pietilä K, Vapalahti O, Pasternack A, Vaheri A (1996) Genetic susceptibility to severe course of nephropathia epidemica caused by Puumala hantavirus. Kidney Int 49(1):217–221CrossRefPubMed Mustonen J, Partanen J, Kanerva M, Pietilä K, Vapalahti O, Pasternack A, Vaheri A (1996) Genetic susceptibility to severe course of nephropathia epidemica caused by Puumala hantavirus. Kidney Int 49(1):217–221CrossRefPubMed
6.
go back to reference Mustonen J, Partanen J, Kanerva M, Pietilä K, Vapalahti O, Pasternack A, Vaheri A (1998) Association of HLA B27 with benign clinical course of nephropathia epidemica caused by Puumala hantavirus. Scand J Immunol 47(3):277–279CrossRefPubMed Mustonen J, Partanen J, Kanerva M, Pietilä K, Vapalahti O, Pasternack A, Vaheri A (1998) Association of HLA B27 with benign clinical course of nephropathia epidemica caused by Puumala hantavirus. Scand J Immunol 47(3):277–279CrossRefPubMed
7.
go back to reference Forslund T, Saltevo J, Anttinen J, Auvinen S, Brummer-Korvenkontio M, Korhonen A, Poutiainen M (1992) Complications of nephropathia epidemica: three cases. J Intern Med 232(1):87–90CrossRefPubMed Forslund T, Saltevo J, Anttinen J, Auvinen S, Brummer-Korvenkontio M, Korhonen A, Poutiainen M (1992) Complications of nephropathia epidemica: three cases. J Intern Med 232(1):87–90CrossRefPubMed
8.
go back to reference Hautala T, Sironen T, Vapalahti O, Pääkkö E, Särkioja T, Salmela PI, Vaheri A, Plyusnin A, Kauma H (2002) Hypophyseal hemorrhage and panhypopituitarism during Puumala virus infection: magnetic resonance imaging and detection of viral antigen in the hypophysis. Clin Infect Dis 35(1):96–101CrossRefPubMed Hautala T, Sironen T, Vapalahti O, Pääkkö E, Särkioja T, Salmela PI, Vaheri A, Plyusnin A, Kauma H (2002) Hypophyseal hemorrhage and panhypopituitarism during Puumala virus infection: magnetic resonance imaging and detection of viral antigen in the hypophysis. Clin Infect Dis 35(1):96–101CrossRefPubMed
9.
go back to reference Sane T, Färkkilä M (2002) Hypopituitarism and hepatitis as complications of nephropathia epidemica. Duodecim 118(5):457–461PubMed Sane T, Färkkilä M (2002) Hypopituitarism and hepatitis as complications of nephropathia epidemica. Duodecim 118(5):457–461PubMed
10.
go back to reference Settergren B, Boman J, Linderholm M, Wiström J, Hägg E, Arvidsson PA (1992) A case of nephropathia epidemica associated with panhypopituitarism and nephrotic syndrome. Nephron 61(2):234–235CrossRefPubMed Settergren B, Boman J, Linderholm M, Wiström J, Hägg E, Arvidsson PA (1992) A case of nephropathia epidemica associated with panhypopituitarism and nephrotic syndrome. Nephron 61(2):234–235CrossRefPubMed
11.
go back to reference Valtonen M, Kauppila M, Kotilainen P, Lähdevirta J, Svartbäck CM, Kosunen O, Nurminen J, Sarkkinen H, Brummer-Korvenkontio M (1995) Four fatal cases of nephropathia epidemica. Scand J Infect Dis 27(5):515–517CrossRefPubMed Valtonen M, Kauppila M, Kotilainen P, Lähdevirta J, Svartbäck CM, Kosunen O, Nurminen J, Sarkkinen H, Brummer-Korvenkontio M (1995) Four fatal cases of nephropathia epidemica. Scand J Infect Dis 27(5):515–517CrossRefPubMed
12.
go back to reference Hullinghorst RL, Steer A (1953) Pathology of epidemic hemorrhagic fever. Ann Intern Med 38(1):77–101PubMed Hullinghorst RL, Steer A (1953) Pathology of epidemic hemorrhagic fever. Ann Intern Med 38(1):77–101PubMed
13.
go back to reference Lukes RJ (1954) The pathology of thirty-nine fatal cases of epidemic hemorrhagic fever. Am J Med 16(5):639–650CrossRefPubMed Lukes RJ (1954) The pathology of thirty-nine fatal cases of epidemic hemorrhagic fever. Am J Med 16(5):639–650CrossRefPubMed
14.
go back to reference Stojanovic M, Pekic S, Cvijovic G, Miljic D, Doknic M, Nikolic-Djurovic M, Micic D, Hrvacevic R, Nesic V, Popovic V (2008) High risk of hypopituitarism in patients who recovered from hemorrhagic fever with renal syndrome. J Clin Endocrinol Metab 93(7):2722–2728CrossRefPubMed Stojanovic M, Pekic S, Cvijovic G, Miljic D, Doknic M, Nikolic-Djurovic M, Micic D, Hrvacevic R, Nesic V, Popovic V (2008) High risk of hypopituitarism in patients who recovered from hemorrhagic fever with renal syndrome. J Clin Endocrinol Metab 93(7):2722–2728CrossRefPubMed
15.
go back to reference Kanerva M, Mustonen J, Vaheri A (1998) Pathogenesis of Puumala and other hantavirus infections. Rev Med Virol 8(2):67–86CrossRefPubMed Kanerva M, Mustonen J, Vaheri A (1998) Pathogenesis of Puumala and other hantavirus infections. Rev Med Virol 8(2):67–86CrossRefPubMed
16.
go back to reference Imura H, Fukata J (1994) Endocrine-paracrine interaction in communication between the immune and endocrine systems. Activation of the hypothalamic-pituitary-adrenal axis in inflammation. Eur J Endocrinol 130(1):32–37CrossRefPubMed Imura H, Fukata J (1994) Endocrine-paracrine interaction in communication between the immune and endocrine systems. Activation of the hypothalamic-pituitary-adrenal axis in inflammation. Eur J Endocrinol 130(1):32–37CrossRefPubMed
17.
go back to reference Turnbull AV, Rivier CL (1999) Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 79(1):1–71PubMed Turnbull AV, Rivier CL (1999) Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 79(1):1–71PubMed
18.
go back to reference Vapalahti O, Lundkvist Å, Kallio-Kokko H, Paukku K, Julkunen I, Lankinen H, Vaheri A (1996) Antigenic properties and diagnostic potential of Puumala virus nucleocapsid protein expressed in insect cells. J Clin Microbiol 34(1):119–125PubMed Vapalahti O, Lundkvist Å, Kallio-Kokko H, Paukku K, Julkunen I, Lankinen H, Vaheri A (1996) Antigenic properties and diagnostic potential of Puumala virus nucleocapsid protein expressed in insect cells. J Clin Microbiol 34(1):119–125PubMed
19.
go back to reference Sjölander KB, Elgh F, Kallio-Kokko H, Vapalahti O, Hägglund M, Palmcrantz V, Juto P, Vaheri A, Niklasson B, Lundkvist Å (1997) Evaluation of serological methods for diagnosis of Puumala hantavirus infection (nephropathia epidemica). J Clin Microbiol 35(12):3264–3268PubMed Sjölander KB, Elgh F, Kallio-Kokko H, Vapalahti O, Hägglund M, Palmcrantz V, Juto P, Vaheri A, Niklasson B, Lundkvist Å (1997) Evaluation of serological methods for diagnosis of Puumala hantavirus infection (nephropathia epidemica). J Clin Microbiol 35(12):3264–3268PubMed
20.
go back to reference Westman P, Kuismin T, Partanen J, Koskimies S (1993) An HLA-DR typing protocol using group-specific PCR-amplification followed by restriction enzyme digests. Eur J Immunogenet 20(2):103–109CrossRefPubMed Westman P, Kuismin T, Partanen J, Koskimies S (1993) An HLA-DR typing protocol using group-specific PCR-amplification followed by restriction enzyme digests. Eur J Immunogenet 20(2):103–109CrossRefPubMed
21.
go back to reference Baskin HJ, Cobin RH, Duick DS, Gharib H, Guttler RB, Kaplan MM, Segal RL; American Association of Clinical Endocrinologists (2002) American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 8(6):457–469PubMed Baskin HJ, Cobin RH, Duick DS, Gharib H, Guttler RB, Kaplan MM, Segal RL; American Association of Clinical Endocrinologists (2002) American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 8(6):457–469PubMed
22.
go back to reference Jurney TH, Cockrell JL Jr, Lindberg JS, Lamiell JM, Wade CE (1987) Spectrum of serum cortisol response to ACTH in ICU patients. Correlation with degree of illness and mortality. Chest 92(2):292–295CrossRefPubMed Jurney TH, Cockrell JL Jr, Lindberg JS, Lamiell JM, Wade CE (1987) Spectrum of serum cortisol response to ACTH in ICU patients. Correlation with degree of illness and mortality. Chest 92(2):292–295CrossRefPubMed
23.
go back to reference Spratt DI, Cox P, Orav J, Moloney J, Bigos T (1993) Reproductive axis suppression in acute illness is related to disease severity. J Clin Endocrinol Metab 76(6):1548–1554CrossRefPubMed Spratt DI, Cox P, Orav J, Moloney J, Bigos T (1993) Reproductive axis suppression in acute illness is related to disease severity. J Clin Endocrinol Metab 76(6):1548–1554CrossRefPubMed
24.
go back to reference Bauer AG, Wilson JH, Lamberts SW (1980) The kidney is the main site of prolactin elimination in patients with liver disease. J Clin Endocrinol Metab 51(1):70–73CrossRefPubMed Bauer AG, Wilson JH, Lamberts SW (1980) The kidney is the main site of prolactin elimination in patients with liver disease. J Clin Endocrinol Metab 51(1):70–73CrossRefPubMed
25.
go back to reference Whitworth JA, Stewart PM, Burt D, Atherden SM, Edwards CR (1989) The kidney is the major site of cortisone production in man. Clin Endocrinol (Oxf) 31(3):355–361CrossRef Whitworth JA, Stewart PM, Burt D, Atherden SM, Edwards CR (1989) The kidney is the major site of cortisone production in man. Clin Endocrinol (Oxf) 31(3):355–361CrossRef
26.
go back to reference Gray A, Feldman HA, McKinlay JB, Longcope C (1991) Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 73(5):1016–1025CrossRefPubMed Gray A, Feldman HA, McKinlay JB, Longcope C (1991) Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 73(5):1016–1025CrossRefPubMed
27.
go back to reference Härkönen K, Huhtaniemi I, Mäkinen J, Hübler D, Irjala K, Koskenvuo M, Oettel M, Raitakari O, Saad F, Pöllänen P (2003) The polymorphic androgen receptor gene CAG repeat, pituitary-testicular function and andropausal symptoms in ageing men. Int J Androl 26(3):187–194CrossRefPubMed Härkönen K, Huhtaniemi I, Mäkinen J, Hübler D, Irjala K, Koskenvuo M, Oettel M, Raitakari O, Saad F, Pöllänen P (2003) The polymorphic androgen receptor gene CAG repeat, pituitary-testicular function and andropausal symptoms in ageing men. Int J Androl 26(3):187–194CrossRefPubMed
28.
go back to reference Bjoro T, Holmen J, Krüger O, Midthjell K, Hunstad K, Schreiner T, Sandnes L, Brochmann H (2000) Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT). Eur J Endocrinol 143(5):639–647CrossRefPubMed Bjoro T, Holmen J, Krüger O, Midthjell K, Hunstad K, Schreiner T, Sandnes L, Brochmann H (2000) Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT). Eur J Endocrinol 143(5):639–647CrossRefPubMed
29.
go back to reference Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE (2002) Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87(2):489–499CrossRefPubMed Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE (2002) Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 87(2):489–499CrossRefPubMed
30.
go back to reference Vanderpump MPJ (2005) The epidemiology of thyroid diseases. JB Lippincott-Raven, Philadelphia, pp 398–406 Vanderpump MPJ (2005) The epidemiology of thyroid diseases. JB Lippincott-Raven, Philadelphia, pp 398–406
32.
go back to reference McGahan JP, Goldberg BB (2008) Diagnostic ultrasound. Informa Healthcare, New York-London McGahan JP, Goldberg BB (2008) Diagnostic ultrasound. Informa Healthcare, New York-London
33.
go back to reference Avsic-Zupanc T, Petrovec M, Furlan P, Kaps R, Elgh F, Lundkvist Å (1999) Hemorrhagic fever with renal syndrome in the Dolenjska region of Slovenia—a 10-year survey. Clin Infect Dis 28(4):860–865CrossRefPubMed Avsic-Zupanc T, Petrovec M, Furlan P, Kaps R, Elgh F, Lundkvist Å (1999) Hemorrhagic fever with renal syndrome in the Dolenjska region of Slovenia—a 10-year survey. Clin Infect Dis 28(4):860–865CrossRefPubMed
34.
go back to reference Markotić A, Nichol ST, Kuzman I, Sanchez AJ, Ksiazek TG, Gagro A, Rabatić S, Zgorelec R, Avsic-Zupanc T, Beus I, Dekaris D (2002) Characteristics of Puumala and Dobrava infections in Croatia. J Med Virol 66(4):542–551CrossRefPubMed Markotić A, Nichol ST, Kuzman I, Sanchez AJ, Ksiazek TG, Gagro A, Rabatić S, Zgorelec R, Avsic-Zupanc T, Beus I, Dekaris D (2002) Characteristics of Puumala and Dobrava infections in Croatia. J Med Virol 66(4):542–551CrossRefPubMed
35.
go back to reference Kim NH, Cho JG, Ahn YK, Lee SU, Kim KH, Cho JH, Kim HG, Kim W, Jeong MH, Park JC, Kang JC (2001) A case of torsade de pointes associated with hypopituitarism due to hemorrhagic fever with renal syndrome. J Korean Med Sci 16(3):355–359PubMed Kim NH, Cho JG, Ahn YK, Lee SU, Kim KH, Cho JH, Kim HG, Kim W, Jeong MH, Park JC, Kang JC (2001) A case of torsade de pointes associated with hypopituitarism due to hemorrhagic fever with renal syndrome. J Korean Med Sci 16(3):355–359PubMed
36.
go back to reference Park JE, Pyo HJ (1996) Delayed onset of diuresis in a patient with acute renal failure due to hemorrhagic fever with renal syndrome who also developed anterior hypopituitarism. Clin Nephrol 46(2):141–145PubMed Park JE, Pyo HJ (1996) Delayed onset of diuresis in a patient with acute renal failure due to hemorrhagic fever with renal syndrome who also developed anterior hypopituitarism. Clin Nephrol 46(2):141–145PubMed
37.
go back to reference Pekic S, Cvijovic G, Stojanovic M, Kendereski A, Micic D, Popovic V (2005) Hypopituitarism as a late complication of hemorrhagic fever. Endocrine 26(2):79–82CrossRefPubMed Pekic S, Cvijovic G, Stojanovic M, Kendereski A, Micic D, Popovic V (2005) Hypopituitarism as a late complication of hemorrhagic fever. Endocrine 26(2):79–82CrossRefPubMed
38.
go back to reference Suh DC, Park JS, Park SK, Lee HK, Chang KH (1995) Pituitary hemorrhage as a complication of hantaviral disease. AJNR Am J Neuroradiol 16(1):175–178PubMed Suh DC, Park JS, Park SK, Lee HK, Chang KH (1995) Pituitary hemorrhage as a complication of hantaviral disease. AJNR Am J Neuroradiol 16(1):175–178PubMed
39.
go back to reference Ahlm C, Lindén C, Linderholm M, Alexeyev OA, Billheden J, Elgh F, Fagerlund M, Zetterlund B, Settergren B (1998) Central nervous system and ophthalmic involvement in nephropathia epidemica (European type of haemorrhagic fever with renal syndrome). J Infect 36(2):149–155CrossRefPubMed Ahlm C, Lindén C, Linderholm M, Alexeyev OA, Billheden J, Elgh F, Fagerlund M, Zetterlund B, Settergren B (1998) Central nervous system and ophthalmic involvement in nephropathia epidemica (European type of haemorrhagic fever with renal syndrome). J Infect 36(2):149–155CrossRefPubMed
40.
go back to reference Alexeyev OA, Morozov VG (1995) Neurological manifestations of hemorrhagic fever with renal syndrome caused by Puumala virus: review of 811 cases. Clin Infect Dis 20(2):255–258PubMed Alexeyev OA, Morozov VG (1995) Neurological manifestations of hemorrhagic fever with renal syndrome caused by Puumala virus: review of 811 cases. Clin Infect Dis 20(2):255–258PubMed
41.
go back to reference Bergmann F, Krone B, Bleich S, Prange H, Paulus W (2002) Encephalitis due to a hantavirus infection. J Infect 45(1):58–59CrossRefPubMed Bergmann F, Krone B, Bleich S, Prange H, Paulus W (2002) Encephalitis due to a hantavirus infection. J Infect 45(1):58–59CrossRefPubMed
42.
43.
go back to reference Mähönen SM, Sironen T, Vapalahti O, Pääkkö E, Hautala N, Ilonen J, Glumoff V, Vainio O, Kauma H, Vaheri A, Plyusnin A, Hautala T (2007) Puumala virus RNA in cerebrospinal fluid in a patient with uncomplicated nephropathia epidemica. J Clin Virol 40(3):248–251CrossRefPubMed Mähönen SM, Sironen T, Vapalahti O, Pääkkö E, Hautala N, Ilonen J, Glumoff V, Vainio O, Kauma H, Vaheri A, Plyusnin A, Hautala T (2007) Puumala virus RNA in cerebrospinal fluid in a patient with uncomplicated nephropathia epidemica. J Clin Virol 40(3):248–251CrossRefPubMed
44.
go back to reference Schaefer S, Boegershausen N, Meyer S, Ivan D, Schepelmann K, Kann PH (2008) Hypothalamic-pituitary insufficiency following infectious diseases of the central nervous system. Eur J Endocrinol 158(1):3–9CrossRefPubMed Schaefer S, Boegershausen N, Meyer S, Ivan D, Schepelmann K, Kann PH (2008) Hypothalamic-pituitary insufficiency following infectious diseases of the central nervous system. Eur J Endocrinol 158(1):3–9CrossRefPubMed
Metadata
Title
Hormonal deficiencies during and after Puumala hantavirus infection
Authors
S. Mäkelä
P. Jaatinen
M. Miettinen
J. Salmi
I. Ala-Houhala
H. Huhtala
M. Hurme
I. Pörsti
A. Vaheri
J. Mustonen
Publication date
01-06-2010
Publisher
Springer-Verlag
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 6/2010
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-010-0918-y

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