Parathyroid hormone (PTH) 1-34 replacement therapy with teriparatide (Forteo, Eli Lilly) may represent a valuable tool to manage mental and physical health in chronic postsurgical hypoparathyroidism, according to the largest study of its kind.
Published online in the Journal of Clinical Endocrinology & Metabolism on July 21, the study investigated the effects of 6 months of treatment with teriparatide in adult subjects with postoperative hypoparathyroidism. Of note, the research, led by Dr Andrea Palermo (University Campus Bio-Medico, Rome, Italy), tested the effect of teriparatide on quality of life for the first time.
The researchers found a "significant and quick increase in serum calcium levels despite a significant reduction in calcium and vitamin D supplementation," reported Dr Palermo. Quality of life showed improvement in all eight domains assessed.
Dr Palermo explained that, until recently, the only therapies approved by the Food and Drug Administration (FDA) for hypoparathyroidism from any cause were calcium and vitamin D (calcitriol) but that this conventional therapy does not work for all patients.
Teriparatide is approved for use in severe osteoporosis but is not approved for the treatment of hypoparathyroidism, reportedly due to adverse findings in animal studies of long-term supraphysiological doses. However, another recombinant parathyroid hormone product (PTH[1-84]) (Natpara, NPS Pharmaceuticals) has recently been approved in the United States for severe hypoparathyroidism.
In this study, Dr Palermo and his colleagues confirmed that "replacement therapy with recombinant (PTH) 1-34 [teriparatide] seems to be an attractive option for those patients who do not stably maintain their serum calcium in the target range," he told Medscape Medical News. But he added that further prospective, longer, and larger studies were needed to evaluate safety of PTH(1-34).
Reinforcing the motivation for their study, Dr Palermo pointed out: "Hypoparathyroid patients who do not respond to conventional therapy experience a very low quality of life." Patients with chronic hypoparathyroidism, and in particular, those who do not respond to calcium and vitamin D supplementation especially in large quantities, have an increased risk of hypercalciuria, hyperphosphatemia, nephrocalcinosis, urolithiasis, and ectopic soft-tissue calcification.
PTH(1-34) Significantly Increased Levels of Serum Calcium
Hypoparathyroidism is a rare mineral metabolism disorder characterized by hypocalcemia, hyperphosphatemia, and deficient parathyroid hormone, which can be congenital or due to the accidental removal or irreversible damage of the parathyroid glands after thyroidectomy
In this study, all 42 patients had postsurgical hypoparathyroidism with serum calcium levels below the lowest normal value at baseline despite ongoing replacement therapy with calcium carbonate of approximately 3000 mg/day or more and a high dosage of calcitriol. The trial was open label because the researchers were able to enroll only patients resistant to calcium and/or vitamin D supplements so that the Italian government would cover the PTH(1–34) therapy expenses.
Of the patients, 90% were women, with an age range of 34 to 77 years. They self-administered PTH(1–34) twice-daily as a 20-μg subcutaneous injection.
The main objective was to bring the adjusted serum calcium level back to normal range, avoiding hypercalcemia. Patients were assessed at 0, 3, and 6 months for levels of calcium intake, serum calcium level, phosphate, creatinine, alkaline phosphatase, and uric acid. In addition to these time points, serum calcium was measured 15 days after the start of PTH(1–34) treatment in order to assess whether calcium/calcitriol supplementation could be reduced.
Quality of life was assessed using the 36-Item Short Form (SF-36) Health Survey before and after 6 months of treatment with PTH(1–34). Eight domains were included in the quality-of-life evaluation: physical functioning, role limitations caused by physical health problems, bodily pain, perception of general health, vitality, social functioning, role limitations due to emotional health problems, and mental health.
Dr Palermo's study is a 2-year prospective open-label study, and the current paper reports the results after the first 6 months of PTH(1–34) treatment.
Mean serum calcium levels significantly increased from baseline to 15 days (7.6 mg/dL vs 9.1 mg/dL, P <P .001) and remained stable until the end of the observational period (6 months), despite a significant reduction in calcium and vitamin D supplementation.
Serum phosphate levels gradually decreased from baseline to 6 months of treatment (P = .005 for trend): after 15 days of therapy (4.3 mg/dL vs 3.8 mg/dL, P = .03) and at 5 months (3.9 mg/dL; P = .019 vs baseline); alkaline phosphatase levels increased (P < .001).
Data from SF-36 showed a significant improvement in the mean scores of all eight domains evaluated (P < .001).
Dr Palermo highlighted that the results were particularly important for patients who could not reach normal calcium levels with conventional therapy and consequently experienced a very low quality of life.
"They can suffer cramps; tetany; seizures; tingling and burning sensation of the fingertips, toes, and lips; and muscle spasms around the mouth and patchy hair loss; all of which are linked to hypocalcemia. In addition, fatigue, anxiety, or depression means these patients find it hard to live a normal social and/or working life.
"For these patients, a subcutaneous, twice-daily 20-μg injection of PTH(1-34) in the abdomen seems to improve both mental and physical health, including fatigue, anxiety, or depression, and general wellness," he noted.
Calcium and calcitriol supplementation before treatment and after 6 months of PTH(1-34) treatment showed a significant reduction in both supplements from 4 g/day to 1.1 g/day (P < .001) and 0.8 μg/day to 0.3 μg/day (P < .001), respectively.
Proof That a Fragment of PTH Can Benefit Hypoparathyroidism
International guidelines suggest that treatment be targeted to maintain serum calcium level (albumin-adjusted total calcium or ionized calcium) in the lower part of the lower limit of the reference range with patients being free of symptoms or signs of hypocalcemia.
After FDA approval earlier this year, the European Medicines Agency (EMA) is still evaluating PTH(1-84).
"This is another proof that PTH or one of its fragments (1-34) can increase calcium level and might improve quality of life in patients with chronic hypoparathyroidism," concluded Dr Palermo.
Recently, the European Society of Endocrinology (ESE) published a new guideline on how best to monitor and treat chronic hypoparathyroidism, as reported by Medscape Medical News.
The authors report they have no relevant financial relationships.
J Clin Endocrinol Metab. Published online July 21, 2015. Article
Medscape Medical News © 2015 WebMD, LLC
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Cite this: Teriparatide Manages Surgical Hypoparathyroidism - Medscape - Aug 06, 2015.