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High Risk of Hypopituitarism in Patients Who Recovered from Hemorrhagic Fever with Renal Syndrome

Neuroendocrine Unit (M.S., S.P., G.C., D.Mil., M.D., M.N.-D., D.Mic., V.P.), Institute of Endocrinology, Diabetes and Diseases of Metabolism, University Clinical Center, Department of Nephrology (R.H.), Military Medical Academy, and Institute of Nephrology (V.N.), University Clinical Center, 11000 Belgrade, Serbia

Address all correspondence and requests for reprints to: Professor Vera Popovic, M.D., Ph.D., F.R.C.P., Neuroendocrine Unit, Institute of Endocrinology, University Clinical Center, Dr Subotica 13, 11000 Belgrade, Serbia. E-mail: popver{at}eunet.yu.

Context: Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses, is a severe systemic infection, with acute shock, vascular leakage, hypotension, and acute renal failure. Pituitary ischemia/infarction and necrosis are known causes of hypopituitarism, often remaining unrecognized due to subtle clinical manifestations. Cases of hypopituitarism after HFRS were previously only sporadically reported.

Objective: The aim of this study was to determine, for the first time, the prevalence of hypopituitarism among HFRS survivors.

Subjects and Methods: In 60 adults (aged 35.8±1.3 yr) who recovered from HFRS 3.7 ± 0.5 yr ago (median 2 yr), assessment of serum T₄, free T₄, TSH, IGF-I, prolactin, cortisol, and testosterone (in males) was followed by insulin tolerance test and/or GHRH+GH-releasing peptide-6 stimulation tests.

Results: Severe GH deficiency was confirmed in eight of 60 patients (13.3%): in five with multiple pituitary hormone deficiencies (MPHDs) and isolated in three. Thyroid axis deficiency was confirmed in five of 60 patients (8.3%), all with MPHD. Hypothalamus-pituitary-adrenal axis deficiency was observed in six of 60 (10.0%); in five with MPHD and isolated in one. Gonadal axis deficiency was confirmed in seven of 56 male subjects (12.5%): five with MPHD and isolated in two. Overall six patients (10.0%) had a single pituitary deficit (three GH, two gonadal, and one adrenal), and five (8.3%) had MPHD. The prevalence of patients having any endocrine deficiency was 18% (11 of 60).

Conclusion: A high prevalence of hypopituitarism after recovery from HFRS is identified, with magnetic resonance imaging revealing atrophic pituitary and empty sella. Awareness is raised to neuroendocrine consequences of HFRS because unrecognized hypopituitarism significantly affects the physical and psychological well-being.