Spontaneous Resolution of Primary Hyperparathyroidism Following COVID-19 Infection

Background: Spontaneous resolution of primary hyperparathyroidism (PHPT) is extremely rare, and has previously been reported exclusively in the setting of apoplexy (auto-infarction) of a large parathyroid adenoma outgrowing its blood supply. We report an unusual case of spontaneous PHPT resolution after Covid-19 infection. Clinical Case: A 38-year-old Hispanic woman was seen in clinic for evaluation of hypercalcemia first noted on routine bloodwork in 2018. She had a history of nephrolithiasis (1 episode) but no other symptom associated with hypercalcemia. She was not on medications associated with hypercalcemia, and had no family history of Ca disorder. Serum biochemistry was notable for hypercalcemia (Ca: 10.9, 10.5, and 10.8 mg/dL, nl 8.4–10.2), normal albumin and Cr, elevated PTH (106 and 70 pg/mL, nl 15–65), with low phosphate (2.3 mg/dL, nl 2.4–4.5) and 25-OH-Vit. D (14 ng/mL, nl 20–80). 24-hr urinary studies showed elevated urine Ca (285 and 375 mg/day, nl 100–250), with urine Cr of 1.3 and 1.5 g/day, respectively. Findings of hypercalcemia, hypercalciuria, and elevated serum PTH, led to the diagnosis of PHPT. Neck ultrasound and sestamibi scan of the parathyroids with SPECT-CT did not localize any abnormal parathyroid gland. A month after PHPT diagnosis, and prior to surgical evaluation, patient presented with a 9-day history of fever, cough, and shortness of breath. She tested positive for Covid-19 infection by SARS-CoV-2 PCR on nasal swab, and was quarantined at home with symptomatic treatment. No glucocorticoids were given. Serum Ca was normal (9.5 mg/dL) at the time of Covid-19 diagnosis. All Covid-19 symptoms subsided 14 days after onset. Repeat labs 1 and 3 months after Covid-19 infection showed persistently normal serum Ca (10.0 and 9.8 mg/dL), with low then normal PTH (13 and 43 pg/mL), compatible with spontaneous resolution of PHPT. Patient denied any neck discomfort before, during, or after Covid-19 infection. Spontaneous resolution of PHPT is rare and follows apoplexy of a large parathyroid adenoma. In our patient, imaging failed to localize a large parathyroid adenoma, making it less likely that resolution of her PHPT was caused by apoplexy. Resolution of PHPT temporally coincided with Covid-19 infection, although the link between the two conditions is unclear at this time. Hypothesized mechanisms include an imbalance in the normal PTH-Ca axis caused by SARS-CoV-2 mediated release of inflammatory cytokines (e.g. interferon, previously reported to lower serum calcium), or development of antibodies against the parathyroid or CaSR. RNA and protein expression of ACE2, the SARS-CoV-2 cell receptor gene, is not detected in normal parathyroid tissue. Conclusion: To our knowledge, this is the first reported case of spontaneous resolution of PHPT after Covid-19 infection. Further studies are needed to understand the frequency of this occurrence, and the underlying mechanism.