ESPE Abstracts

Introduction: Tuberous sclerosis (TS) is a rare, autosomal dominant, multisystem disease with a frequency of 1:6,000-10,000. It is caused by variants in the genes encoding hamartin (TSC 1) and tuberin (TSC 2) that normally act as inhibitors of the mTOR signaling cascade that regulates cell proliferation and migration, angiogenesis, and cell metabolism. The most frequent clinical presentation includes hypochromic macules, angiofibromas, hamartomas in the central nervous system (CNS), renal tumors, and cardiac rhabdomyomas among others. There are few communications of neuroendocrine tumors in TS and their association with primary hyperparathyroidism is very rare, with only 4 cases reported, 2 of them in pediatric patients.

Case report: An 11.5 years old male patient with history of TS confirmed by clinical criteria at 3 years of age (hypochromic macules, hamartoma in the CNS, and mother and sister with TS) was consulted to endocrinology department for the laboratory finding of hypercalcemia. During anamnesis, he referred headache, nicturia and behavioral disorders with self and hetero-aggression. He had weight and height in 50 percentile, peripubertal, blood pressure in 90 percentile and normal EKG. Within diagnostic studies it was requested: -biochemical profile: elevated calcemia (11.3 mg/dl), low phosphatemia (3.3 mg/dl), inadequate elevated PTH for calcemia (49 pg/ml), low 25(OH)D (12.8 ng/ml), normal ALP (296 IU/L), normal renal function, hypercalciuria (436 mg/day: 13 mg/k/day) and low tubular phosphorus reabsorption (86%). -imaging studies: generalized mild osteopenia, absence of periodontal lamina dura and diploe thickening, total body less head densitometry: Z score -2.2 SDS and normal renal ultrasound. Clinical case was consistent with symptomatic primary hyperparathyroidism. Parathyroid ultrasound showed an 8 mm hypoechoic image behind the left thyroid lobe and Sestamibi and Technetium 99 scan with late uptake and thyroid suppression confirmed hyperfunctioning of both superior parathyroid glands. Surgery was performed with identification of both enlarged upper parathyroids and pathology was compatible with hyperplasia. He presented transient post-surgical hypoparathyroidism and during follow up he normalized biochemical profile in 3 weeks.

Conclusions: Primary hyperparathyroidism is very infrequent in pediatrics. Its association with TS is extremely rare. The suspected pathophysiological mechanism could be related with the abnormal proliferation of the parathyroid cells mediated by the lack of inhibition of the mTOR pathway. We suggest evaluating symptoms associated with hypercalcemia and eventual phosphocalcic profile in patients with TS.