Endocrine Abstracts

We present a case of Inactivating PTH/PTHrP signalling disorder (IPPSD) revealed in aduthood in the context of respiratory alkalosis caused by covid-19 infection that led to worsening of the preexisting hypocalcemia and intensification of the usual hypocalcemic symptoms. A 39 year old female with history of subclinical hypothyroidism and bilateral cataracts was admited due to hypoxemia in the context of severe covid-19 infection with bilateral pulmonary infiltrates. She was visiting a Neurologist because of chronic complaints of tingling and cramping, with no visible pathology on the exams so far performed (apart from the basal ganglia calcifications on the brain CT from 2010). On admission she was hypotensive, tachypneic, feverish and complained of paresthesia and acral cramping. Metabolic alkalosis (pH 7.48, pCO2 31 mmHg, pO2 62 mmHg, K⁺ 2.97 mmol/l, Na⁺ 133 mmol/l, Ca²⁺ 0.5 mmol/l) worsened the eletrolyte imbalance leading to severe symptomatic hypocalcemia with prolongued QT segment (500 ms) on the ECG. The initial calcemia (Ca²⁺) was 3.9 mg/dl [8.6-10], P (Phosphate) 4.0 mg/dl [2.5-4.5], 25OH-vitamin D 13 ng/ml, Mg 1.8 mg/dl [1.6-2.6], 1.25(HO)2 vitamin D was normal, PTHI 190 pg/ml [15-65]. After 48 h Ca²⁺ was 6.4, P 6.1, 25OH-vitamin D 18 ng/ml; the patient was discharged with Ca²⁺ of 9.2, P 4.5 and 25OH-vitamin D of 24 ng/ml with the suspition of IPPSD given the protracted history of paresthesia, cataracts and intracerebral calcifications sugesting long standing hypocalcemia. During follow up PTHi ranged 190-347 pg/ml [15-65], Ca²⁺ 6.1-9.2 mg/dl, P 2.7-5.1 mg/dl, 25OH-vitamin D 21-34 ng/ml and she remained assymptomatic and compliant with calcitriol 0.5 mg q12 h, 1500 mg of calcium carbonate 5 times daily and 22400UI colecalciferol montly. Thyroid antibodies were negative and the US normal; the TSH maintained the same subclinical pattern fluctuating from 3 to 8.8 mUI/l. The gonadal axis were not afected. The patients has a BMI of 32 kg/m² though it is not possible to confirm if obesity started at a young age. Hand X-ray showed no brachydactily nor subcutaneuous ossification. Given the clinical suspition for Pseudohipoparathyroidism type 1B, GNAS sequencing was performed but no mutation was found. Nevertheless this clinical IPPSD subtype is more often associated with metilation errors so genetic examination was performed with metilation probes and the genetic mutations were identifyed. Clinical and biochemical manifestations are usually unnoticed during childhood; diagnosis is often delayed owing to lack of recognition of the syndrome. Genetic counseling may facilitate the diagnosis at an early age and prevent the patients from misleading follow-ups or diagnosis and/or engaging extensive unnecessary investigations.