Progressive scarring alopecia due to extensive subcutaneous scalp calcifications in a patient with pseudohypoparathyroidism (PHP)
Gopie SV, Ramakrishnan R, Rao SD, and Thudi V. Progressive scarring alopecia due to extensive subcutaneous scalp calcifications in a patient with pseudohypoparathyroidism (PHP). Endocrine Reviews 2017; 38(3)
Introduction: PHP is a group of heterogeneous disorders defined by targeted end-organ (kidney and bone) unresponsiveness to PTH action and associated with hypocalcemia, hyperphosphatemia and elevated PTH levels. PHP-1 is a rare autosomal dominant disorder that appears to be caused by hypermethylation or mutations of the genes affecting the regulatory elements of GNAS1 (a gene encoding the alpha subunit of the coupled G protein receptor). Although PHP-1A has characteristic phenotypic features, PHP-1 B usually presents with symptoms of hypocalcemia, low bone mineral density and sometimes osteitis fibrosa. We present an unusual patient with PHP-1B, with prolonged relatively asymptomatic hypocalcemia, and intra-cranial and extensive subcutaneous calcifications of the scalp resulting in alopecia. Clinical Case:A 37 year old woman presented to our clinic for management of chronic hypocalcemia and hyperphosphatemia. She gave history of progressive alopecia of the scalp for 5 years, seizures, and hypothyroidism and had a low IQ, and has been in a group home for a number of years. She reported no symptoms of hypocalcemia, had not had seizures recently, and was not taking vitamin D, calcitriol or calcium supplements. She weighed 67.1 kg and stood at 150cm tall with a BMI of 28.9 kg/m2and had none of the phenotypic features of PHPH-1A. Trousseau and negative Chvostek's signs were absent and there were no soft tissue calcifications. However, palpation of the skull revealed a granular/pebble-like feeling. When seen in April 2016 showed her albumin adjusted serum calcium was 5.9 mg/dL (RR: 8.2 - 10.2 mg/dL), ionized calcium 0.80 mmol/L (RR: 1.00 - 1.35 mmol/L), phosphorus 5.3 mg/dL (RR: 2.5 - 4.5 mg/dL), PTH 650 pg/mL (RR: 15 - 65 pg/mL), 25-hydroxyvitamin D of 45 ng/mL (RR: >20 ng/mL), alkaline phosphatase of 167 IU/L, and a creatinine of 0.61 mg/dL (RR: <1.03 mg/dL). Previous labs from EMR from February 2013 showed a serum calcium of 7.9 mg/dL (range: 6.5 - 7.9 mg/dL) and phosphate of 5.7 and 5.3 mg/dl. X-rays of the hands showed osteopenia and normal metacarpals, and CT scan of the head showed diffuse intracranial calcifications (basal ganglia and cerebellum), and diffuse subcutaneous punctate calcifications of the entire scalp. She was started on calcitriol 0.25 mcg twice a day, and calcium carbonate 1000 mg with lunch and 500 mg with dinner. The daily dose of calcitriol was increased to 0.75 mcg, and then to 1.0 mcg. After 2 months, serum calcium had improved to 7.6 mg/dL, ionized calcium 0.99 mmol/L (1.00 - 1.35 mmol/L), phosphorus 4.5 mg/dL (2.5 - 4.5 mg/dL). Conclusion: Although intracranial calcification is a well-known complication of all varieties of hypoparathyroid states, it is less common in pseudo and post-surgical hypoparathyroidism. We believe that extensive sub-cutaneous scalp calcifications caused her progressive scarring alopecia, a finding that has not been reported previously.