SAT218 Refractory Hypocalcemia From Combined Autosomal Dominant Hypocalcemia Type 2 And Postsurgical Hypoparathyroidism
Authors: Sonmez Ince Melda , Hannan Fadil , Helen Esfandiari Nazanene , Hussain Mehboob A , Haymart Megan R , Thakker Rajesh V , Clines Gregory A 
Published: October 2023

Disclosure: M. Sonmez Ince: None. F. Hannan: None. N. Esfandiari: None. M. Hussain: None. M.R. Haymart: None. R.V. Thakker: None. G.A. Clines: None.

Background: Autosomal dominant hypocalcemia type 2 (ADH2), due to activating mutations in GNA11, is a rare disorder that causes hypocalcemia with low or inappropriately normal PTH. Postsurgical hypoparathyroidism (PSHP) is the most common etiology for hypoparathyroidism. The patient described was afflicted by both conditions and had persistent hypocalcemia despite aggressive management. Clinical Case: A 50-year-old female was found to have an enlarged thyroid on exam and subsequently diagnosed with papillary thyroid cancer (PTC). She underwent a total thyroidectomy without parathyroid autotransplantation since parathyroid glands were not identified during intraoperative pathologic survey. Surgical pathologic examination confirmed PTC with the identification of a single and small intrathyroidal parathyroid gland. Due to the patient’s low risk (T1N0M0), radioactive iodine ablation was not performed. Before thyroidectomy, serum corrected calcium was 6.4-8.5 mg/dL (8.6-10.3 mg/dL) and PTH was 9-21 pg/mL (10-65 pg/mL) during the previous 20 years. Following thyroidectomy, the patient had multiple emergency department visits due to hypocalcemia, hand cramping, and paresthesias. The patient was diagnosed with postsurgical hypoparathyroidism: corrected calcium 5.6-6.7 mg/dL, 24-hour urine calcium 112 mg (100-300 mg/24hour), magnesium 1.4-1.9 mg/dL (1.6-2.6 mg/dL), phosphorus 3-8.2 mg/dL (2.7-4.6 mg/dL). PTH remained &lt;6 pg/mL. The patient was then referred to an academic endocrinology. TSH, AM cortisol, 25-vitamin D, iron, ceruloplasmin, copper, and 21-hydroxylase antibody concentrations were normal. Genetic testing revealed a pathogenic GNA11 variant (c.178C&gt;T, p.(Arg60Cys)); no mutations were identified with CASR or AP2S1. Despite aggressive management with total daily oral calcitriol up to 12 mcg daily, calcium 8 grams, and chlorthalidone, the patient required calcium infusions thrice weekly. Despite the addition of teriparatide 20 mcg BID, the patient remained dependent on calcium infusions, with improvement after the addition of IV calcitriol. Recently, continuous teriparatide delivery was started using an Omnipod insulin pump that has significantly reduced the patient’s dependence on calcium infusions with serum calcium that are now 8-9 mg/dL. Conclusion: ADH2, due to gain-of-function mutations of GNA11, that encodes the Gα11 protein, causes life-long hypocalcemia that is often asymptomatic and undiagnosed. We report here the first documented case of combined ADH2 and PSHP. This case highlights that patients with ADH2 likely have hypoplastic parathyroid glands and that caution is required with procedures that may disrupt parathyroid gland function. Furthermore, the refractory nature of this patient’s hypocalcemia may suggest that GNA11 mutations in the kidney and skeleton reduce the effectiveness of standard hypocalcemia treatments.

Presentation: Saturday, June 17, 2023