Endocrine Abstracts

Case: We report a 63-year-old woman who was referred to our Endocrine Bone Unit with difficult to control hypoparathyroidism. Sixteen-years previously, she underwent a total thyroidectomy with radioiodine ablation for multifocal papillary thyroid carcinoma with lymph node involvement. However, surgery was complicated by permanent postsurgical hypoparathyroidism, requiring regular calcium supplementation and active vitamin D (Alfacalcidol 1.25 mg). Over the 10-years prior to referral, corrected calcium values were frequently <2 mmol/l (despite treatment compliance), necessitating up-titration of the Alfacalcidol dose (averaging 1.75 mg daily). However, maintaining a target corrected calcium of 2.1 to 2.2 mmol/l, resulted in hypercalciuria with 24-hour urinary calcium measurements frequently >10 mmol/l (even following introduction of Indapamide and low salt/protein diet), due to the increasing circulating calcium and the permanent loss of PTH-induced active calcium transport in the distal tubule. This was associated with radiological evidence of nephrolithiasis/renal calculi and recurrent episodes of renal colic. Additionally, she had worsening bone mineral density without a history of fragility fractures, secondary to postmenopausal status, previous TSH suppression after thyroid cancer (now in remission), hypercalciuria and maternal osteoporosis history. Bone turnover was not reduced (which can occur where hypoparathyroidism causes adynamic bone) and so based on her fracture risk she was prescribed an oral bisphosphonate. Despite this, bone mineral density fell at both the lumbar spine (T-scores -1.3 to -1.7) and hip (T-scores -2.0 to -2.6).

Outcome: The principal management issues for this patient are: (1) difficult to control hypoparathyroidism, (2) hypercalciuria with nephrolithiasis/renal calculi due to necessary use of calcium/active vitamin D to maintain circulating calcium, (3) worsening bone mineral density. Therefore, given that potent antiresorptive therapies for osteoporosis risk causing hypocalcaemia and adynamic bone in a high-risk patient, a multidisciplinary decision was made to start PTH-analogues (Teriparatide), providing PTH replacement therapy for hypoparathyroidism, anabolic therapy for osteoporosis, and allow a reduction in the Calcium/Alfacalcidol doses.

Discussion: Most cases of secondary hypoparathyroidism are postsurgical with bilateral thyroid surgery the cause in >80% of patients. Conventional therapy involves the titration of calcium/active vitamin D, with the aim of preventing signs and symptoms of hypocalcaemia, maintaining serum calcium levels slightly below normal/low normal range, avoiding hypercalciuria/hypercalcaemia, and avoiding renal calcifications. PTH-analogues as a replacement therapy for hypoparathyroidism provides an additional therapeutic option, particularly for those who remain uncontrolled or those with side-effects of standard treatment (including calcifications).