Hyponatremia and Isolated Free T4 Elevation in a Patient With Acute Intermittent Porphyria

Abstract

Background: Porphyrias represent a spectrum of diseases that stem from dysfunction within the heme biosynthetic pathway. Acute intermittent porphyria (AIP) is the most common type of porphyria due to a genetic deficiency of porphobilinogen deaminase which results in a wide range of neurovisceral symptoms. Hyponatremia and abnormalities with thyroid function have been found in AIP but the mechanisms behind these processes are unclear. Clinical Case: A 26-year-old male with a history of chronic, recurrent abdominal pain presented with 10 days of progressively worsening periumbilical abdominal pain and constipation. He describes that preceding the onset of symptoms he had been binging 5-10 standard alcoholic drinks each day for a few days. Initial laboratory workup demonstrated hyponatremia with Na 114 mmol/L (n: 134 – 137 mmol/L), hypochloremia with Cl 76 mmol/L (n: 95 – 108 mmol/L), and hyperbilirubinemia with total bilirubin 2.5 mg/dL (n: 0.2 – 1.3 mg/dL). CT abdomen/pelvis was negative for any concerning pathology. Further studies showed low serum osmolality at 243 mOsm/kg (n: 275 – 295 mOsm/kg), urine Na 62 mmol/L (n > 20mmol/L), and urine osmolality at 394 mOsm/kg (n: 300 – 900 mOsm/kg) consistent with SIADH. The patient was treated with 3% NaCl and free water restriction to 1.2L/day with improvement in Na levels. Further laboratory workup demonstrated normal TSH, but persistently elevated free T4 with maximum free T4 of 2.77 ng/dL (n: 0.80 – 1.70 ng/dL) which downtrended to 1.99 ng/dL by discharge. Thyroid ultrasound was unremarkable. Pituitary evaluation via hormonal workup and MRI brain was negative for any abnormalities. Given the symptomatology and laboratory findings, the patient was evaluated for porphyria. Laboratory evaluation demonstrated severe elevations in urine porphyrins, urine delta aminolevulinic acid (56.8 mg/24h, n < 4.5 mg/24h), and urine porphobilinogen (82.5 mg/g, n < 2.3 mg/g) consistent with AIP. The patient was treated with four days of hematin infusions which resolved his abdominal pain and was discharged in an improved state. Conclusion: AIP is a rare entity brought out by a deficiency in porphobilinogen deaminase, a key enzyme in the heme biosynthesis pathway. Various metabolic disturbances have been described in AIP including hyponatremia and alterations in thyroid function tests suggestive of thyrotoxicosis. Hyponatremia in our patient was likely due to SIADH from neurovisceral pain. Our patient displayed isolated free T4 elevation as well. We hypothesize this developed due to his acute illness causing a greater decrease in D2 deiodinase activity compared to any concomitant increase in D3 deiodinase activity. This was supported by his free T4 level downtrending following treatment of his AIP attack. More research is needed to further elucidate the mechanism behind these derangements in biochemical markers and their impact on patient prognosis.