Diagnosis and Treatment > Signs and Symptoms
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Summary
In this case report, we present a novel mutation in Lim-homeodomain (LIM-HD) transcription factor, LHX3, manifesting as combined pituitary hormone deficiency (CPHD). This female patient was originally diagnosed in Egypt during infancy with Diamond Blackfan Anemia (DBA) requiring several blood transfusions. Around 10 months of age, she was diagnosed and treated for central hypothyroidism. It was not until she came to the United States around two-and-a-half years of age that she was diagnosed and treated for growth hormone deficiency. Her response to growth hormone replacement on linear growth and muscle tone were impressive. She still suffers from severe global development delay likely due to delay in treatment of congenital central hypothyroidism followed by poor access to reliable thyroid medications. Her diagnosis of DBA was not confirmed after genetic testing in the United States and her hemoglobin normalized with hormone replacement therapies. We will review the patient’s clinical course as well as a review of LHX3 mutations and the associated phenotype.
Learning points:
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Describe an unusual presentation of undertreated pituitary hormone deficiencies in early life
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Combined pituitary hormone deficiency due to a novel mutation in pituitary transcription factor, LHX3
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Describe the clinical phenotype of combined pituitary hormone deficiency due to LHX3 mutations
Search for other papers by Marlene Tarvainen in
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Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
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Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
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Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Division of Internal Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
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Summary
Puumala 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:
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Pituitary haemorrhage resulting in hypopituitarism has been reported during acute HFRS caused by PUUV and other hantaviruses.
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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.
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This case report suggests that the late-onset hypopituitarism and peripheral endocrine defects after HFRS could evolve via autoimmune mechanisms.
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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.
