Autoimmune polyendocrinopathy and hypophysitis after Puumala hantavirus infection

Abstract

SummaryPuumala hantavirus (PUUV) infection causes nephropathia epidemica (NE), a relatively mild form of haemorrhagic fever with renal syndrome (HFRS). Hypophyseal haemorrhage and hypopituitarism have been described in case reports on patients with acute NE. Chronic hypopituitarism diagnosed months or years after the acute illness has also been reported, without any signs of a haemorrhagic aetiology. The mechanisms leading to the late-onset hormonal defects remain unknown. Here, we present a case of NE-associated autoimmune polyendocrinopathy and hypopituitarism presumably due to autoimmune hypophysitis. Thyroid peroxidase antibody seroconversion occurred between 6 and 12 months, and ovarian as well as glutamate decarboxylase antibodies were found 18 months after acute NE. Brain MRI revealed an atrophic adenohypophysis with a heterogeneous, low signal intensity compatible with a sequela of hypophysitis. The patient developed central (or mixed central and peripheral) hypothyroidism, hypogonadism and diabetes insipidus, all requiring hormonal replacement therapy. This case report suggests that late-onset hormonal defects after PUUV infection may develop by an autoimmune mechanism. This hypothesis needs to be confirmed by prospective studies with sufficient numbers of patients.Learning points:Pituitary haemorrhage resulting in hypopituitarism has been reported during acute HFRS caused by PUUV and other hantaviruses.Central and peripheral hormone deficiencies developing months or years after HFRS have also been found, with an incidence higher than that in the general population. The pathogenesis of these late-onset hormonal defects remains unknown.This case report suggests that the late-onset hypopituitarism and peripheral endocrine defects after HFRS could evolve via autoimmune mechanisms.The sensitivity of current anti-pituitary antibody (APA) tests is low. A characteristic clinical course, together with typical brain MRI and endocrine findings may be sufficient for a non-invasive diagnosis of autoimmune hypophysitis, despite negative APAs.

Hypopituitarism after Orthohantavirus Infection: What is Currently Known?

“…In contrast to acute vascular damage to the pituitary gland, an autoimmune mechanism underlying the pituitary gland problems seen post-orthohantavirus infection could explain a more smothering clinical course. For instance, endocrine disturbances caused by auto-antibodies due to orthohantavirus infection has been suggested in a single case report [17].…”

“…However, clear bleeding of the pituitary gland does not seem to be the underlying mechanism in all of the reported cases of hypopituitarism after orthohantavirus infection. Direct pituitary damage due to orthohantavirus has been identified and published in 28 patients in 11 case-reports and case-series [9,17,36,37,38,39,40,41,42,43,44]. Thus far, impaired function of the posterior lobe of the pituitary has not been described.…”

“…PUUV infection was reported most frequently (14/28 cases) [9,17,38,39,40,43,44]. While one case report discussed DOBV infection [36], in 14 cases (two originating from Korea [37,41] and twelve originating from Serbia [42,43]), a specific orthohantavirus type was not mentioned since diagnosis was made via serology detecting multiple orthohantaviruses.…”

“…In the remaining cases, detection of pituitary damage was delayed varying from a few months to thirteen years after infection [17,38,40,41,42,43]. These patients presented with signs of endocrine disturbances after recovery from orthohantavirus infection.…”

“…Furthermore, one patient suffered initially from hypogonadism and hypothyroidism six months after acute infection. Another six months later this patient developed polydipsia and polyuria due to diabetes insipidus [17].…”