Endocrine Abstracts

Hypocalcaemia, characterized by abnormally low calcium levels, can stem from various aetiologies, broadly classified as parathyroid hormone (PTH) dependent or PTH independent. PTH-dependent causes encompass deficiencies in circulating PTH, either in isolation or as part of complex syndromes or genetic disorders, further categorized into disorders of parathyroid formation, PTH synthesis or secretion disorders, and parathyroid gland destruction disorders. The patient, presenting in his early 30 s with mild symptomatic hypocalcaemia, displayed spectrum of manifestations associated with hypocalcaemia, including weakness, muscle cramps, nervousness, headaches, and hyperexcitability of nerves. Notably, his mother and sister had hypoparathyroidism. Biochemical analysis revealed persistently undetectable PTH levels, corrected calcium of 1.88 mmol/l, vitamin D of 101 nmol/l, GFR of 80 ml/min, HbA1 C of 41, and 24-hour urine calcium of 10.4 mmol/day (normal range: 2.5-8). Despite management strategies involving Vitamin D analogues and calcium supplements to maintain optimal serum calcium levels between 2 to 2.2 mmol/l, patient continued to experience hypercalciuria, leading to recurrent kidney stones. Introducing Bendroflumethiazide to counter tubular excretion of calcium proved unsuccessful, prompting need for ongoing endocrinology follow-up to monitor hypocalcaemia and adjust medications. Genetic testing eventually revealed a heterozygous AIRE mutation, unveiling a compelling case of hypoparathyroidism attributed to autoimmune destruction of the parathyroid gland, specifically associated with autoimmune poly endocrinopathy candidiasis ectodermal dystrophy (APECED) or Autoimmune Polyglandular Syndrome type 1 (APS1). APS1, an autosomal recessive disorder linked to mutations in the AIRE gene on Chromosome 21q22.3, Intriguingly, genetic testing revealed a heterozygous AIRE mutation, presenting an autosomal dominant pattern that suggests the potential existence of an unidentified AIRE variant or more probable that symptoms are unrelated to AIRE variant. Classic triad characterizing APS1—mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency— often accompanied by enamel hypoplasia, alopecia, vitiligo, pneumonitis, hepatitis, autoimmune gastritis, and enteropathy. However, in this instance, patient solely presented with hypoparathyroidism, emphasizing importance of considering APS1 in individuals under 30 with hypoparathyroidism, even if a singular component of the triad is evident. This illustrative case underscores intricate landscape of familial hypoparathyroidism, encompassing genetic complexities and formidable challenge of managing associated complications. It accentuates the imperative of a holistic and individualized approach, integrating genetic analysis, symptom surveillance, and tailored therapeutic interventions. The persistence of hypercalciuria and kidney stones underscores the need for continued vigilance and adaptation of management strategies for optimal patient care.