SAT581 Parathyroid Hormone Related Protein-induced Hypercalcemia In Medullary Thyroid Carcinoma In Pediatric Patient With MEN2A
Authors: Ackah Sarah Adjepomaa , DiMeglio Linda A , Sanchez Juan C , Geddes Gabriella C 
Published: October 2023

Abstract
Disclosure: S.A. Ackah: None. L.A. DiMeglio: None. J.C. Sanchez: None. G.C. Geddes: None.
Background: PTHrp is a well-known cause of hypercalcemia of malignancy. Although PTHrp can often be detected in papillary, follicular and anaplastic thyroid cancers it does not always lead to hypercalcemia. Okotur 2007 described PTHrp in an adult medullary thyroid carcinoma (MTC). No pediatric cases have been described. Case: 8 year old female presented on transfer from hospital in Kenya where she had been admitted for three months with diarrhea and malnourishment (weight Z-score -6.5). She had been initially treated for aspiration pneumonia with negative testing for HIV, tuberculosis, stool cultures and parasites. At our facility, chest, abdomen and pelvis imaging were interpreted as an abscess from perforated appendicitis, bilateral hydroureteronephrosis, bilateral multifocal pneumonia and coronary artery ectasia. She experienced respiratory status decline requiring intubation. Further work up included consults and testing by infectious disease, genetics, immunology, cardiology, gastroenterology, pulmonology, and urology. In Kenya, the patient was initially normocalcemic and the calcium then slowly increased, so that on admission to our facility was found to have calcium 18.3 mg/dL (8.5-10.5), phosphorous 3.3 mg/dL (3.4-5.5), Creatinine 0.3 mg/dL (0.3-0.8), albumin 3.5 g/dL (3.5-4.7), PTH 5 pg/mL(10-65), TSH 1.9 mIU/ml (0.4-4.2), Free T4 0.8 ng/dL(0.6-1.5). IV hydration and pamidronate 0.5 mg/kg x 3 days administration resolved the hypercalemia. Rapid whole genome testing revealed a de novo pathogenic variant in RET (RET NM_020975.6 c.2753T&gt;C; p.M918T) previously reported in individuals with MEN type 2A and 2B phenotypes. Thyroid ultrasound showed 2 nodules. FNA of both showed MTC; MTC was also present on lung biopsy. Screening labs obtained then showed PTHrp 301 pmol/L(adult range 0.0-3.4), Calcitonin 1433 pg/mL(0.0-5.1), VIP &lt;13 pg/mL(0-60), Gastrin 45 pg/mL(0-100), Chromogranin A 4049 ng/mL(0-103), CEA123.7 ng/mL(0.0-2.5), metanephrine 0.91 nmol/L(0.00-0.49), normetanephrine 0.48 nmol/L(0.00-0.89). Bone scan showed diffusely diminished physiological uptake in the growth plates and diffuse bilateral lung uptake. Due to concern about ability to tolerate thyroidectomy, the patient was begun on selpercatinib, an oral chemotherapeutic agent specifically for tumors with disruption of RET gene. On day 11 of treatment, she was extubated to noninvasive respiratory support. Now, 3 months out from pamidronate and her hypercalcemia has not recurred. Conclusions: Hypercalcemia in pediatric patients with low PTH should prompt further workup including PTHrP measurement. In this case, we report a case of a child with MEN 2A and metastasized MTC with hypercalcemia attributable to PTHrp secretion.
References: Okutur, et al, Hypercalcemia of Malignancy Induced by PTHrPp in a Patient with MTC. İnönü Üniversitesi Tıp Fakültesi Dergisi. 2007; 14(4) 263-266 (2007).
Presentation: Saturday, June 17, 2023