Abstract Disclosure: M. Yabe: None. Z. Lin: None. F. Joseph: None. G. Philip: None. R. Silver: None. L. Callejas: None. J. Giunta: None. Untreated syphilis is on the rise in the United States. The CDC reported syphilis cases in newborns have increased 10-fold over a decade in November 2023, signifying the emergence of untreated infections. Pituitary involvement in syphilis is a very rare phenomenon, and endocrinological investigation is often overlooked. This will be the second reported case of neurosyphilis with pituitary involvement in a non-HIV infected patient. A 45-year-old female with no significant past medical history was admitted to the hospital with progressive neurological symptoms of intermittent left-side headache, hearing loss with tinnitus, and gait instability. Postcontrast MRI Brain revealed multifocal leptomeningeal enhancement involving supratentorial and infratentorial regions. Thickening of the enhanced pituitary infundibulum was also noted. Subsequent RPR titer showed 1:16 and lumbar puncture revealed CSF-VDRL titer 1:32, with pleocytosis 83 cells/uL, CSF-glucose 19 mg/dL, and CSF-protein 370 mg/dL. The patient completed Penicillin G 4 million/units intravenous every 4 hours for 14 days, with repeat MRI showing significant interval decrease in previously described extensive supratentorial and infratentorial leptomeningeal enhancement. However, there is no record of her sexual partner receiving treatment. The patient was readmitted one year later after a fall while displaying dysmetria. MRI Brain with contrast revealed a small subacute infarct along the right frontal corona radiata and pituitary gland measuring up to 1.2 cm in craniocaudal dimension compared to 0.4 cm on the prior exam. This prompted evaluation of pituitary hormones: FSH 0.8 IU/L, LH <0.3 IU/L, and ACTH 6.3 pg/mL, with normal serum growth hormone and prolactin levels. Further investigation revealed morning cortisol 2.5 ug/dL, thyrotropin < 0.2 uIU/mL, and free thyroxine 0.63 ng/dL. Radiological evidence is suspicious of inflammatory etiology of the pituitary gland. The patient was discharged with endocrinology follow-up and plan to perform a pituitary gland biopsy as an outpatient for confirmatory result. The association of neurosyphilis and hypophysitis leading to panhypopituitarism in a non-HIV infected patient was first reported in 2015. Since then, there remains limited research regarding their association due to rarity of pituitary involvement in neurosyphilis. With untreated syphilis on the rise and increased availability of MRI, clinicians should expect to encounter more cases of neurosyphilis with pituitary involvement in the future. Early detection of panhypopituitarism in those with positive CSF-VDRL titer could lead to better clinical outcomes. It is paramount that these cases are documented to emphasize pituitary involvement in neurosyphilis and encourage a low threshold to initiate endocrinological testing in the future. Presentation: 6/3/2024
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