Endocrine Abstracts

Introduction: Acquired PTH Resistance (Acquired Pseudohypoparathyroidism) appears to be an extremely rare disease.

Case Report: A 19-year old man with history of brain medulloblastoma treated by surgery, radiotherapy and chemotherapy 9 years earlier was admitted to hospital in 2019 due to new-onset hypocalcemia. Patient presented with muscle cramps in legs, a tingling sensation in hands and feet, numbness around the mouth, and memory disturbances. Previously serum calcium levels were normal. Until the age of 10, psychophysical development was normal. Family history of calcium or PTH abnormalities was negative. Physical examination revealed positive Trousseau’s sign, alopecia, lower limbs paresis, and mental retardation most likely due to the brain cancer. The biochemical evaluation showed low level serum calcium and ionized calcium as follows: 7.9 mg/dl and 0.98 mmol/l, high level phosphorous: 6.8 mg/dl, high level PTH: 780 pg/ml, normal level 25OHD3: 70 ng/ml, low level calcium diurnal urine collection: 41 mg/24 h. There were no other endocrinopathies nor renal and liver failure. Ultrasound examination showed no evidence of nephrolithiasis or nephrocalcinosis and x-ray scans revealed no signs of osteodystrophy. There were no cerebral calcifications. Treatment with calcium carbonate and alphacalcidol was initiated. The symptoms of tetany equivalents subsided and the level of calcium stabilized. PTH levels remained high despite calcium and magnesium normalization. The PTH resistance, probably acquired, was recognized. In the 4-year follow-up, the course of the disease was improved and the doses of vitamin D and calcium carbonate were significantly reduced.

Discussion: Genetic causes of PTH resistance become apparent in early childhood. At discharge, we suggested an acquired form of PTH receptor resistance, perhaps antibody or mutation related. We have no scientific methods to confirm this. Spontaneous improvement of the clinical course and alleviation of disorders in the last 4 years, may also speak in favor of an immunological mechanism. Uremic patients may develop antibodies against the PTH receptor¹. Since the report in NEJM in 2021, we know that an acquired variant of the pseudohypoparathyroidism is possible². The mechanism of the disease in the described patient is unknown, however, drug immunization cannot be ruled out despite the use of old-generation cytotoxic drugs. Tyrosine kinase and immune checkpoint inhibitors were not used. Therefore, further research is needed.

References 1. Juppner H, Bialasiewicz AA, Hesch RD; Lancet 1978; 2: 1222-4.2. Mandl A, Burbelo P, Di Pasquale G at al.; N Engl J Med 2021;385:1974-80