New guidelines on parathyroid hormone disease debut
A pair of clinical guidelines on hypo- and hyperparathyroidism, respectively, had an evening out at the American Society for Bone and Mineral Research (ASBMR) annual meeting on Sunday, allowing attendees to have a preview before their official publication.
For hypoparathyroidism, panel members “suggested” – that is, made a weak recommendation based on low-quality evidence – that most patients receive the long-standing mainstays of treatment, supplements. based on calcium and vitamin D, as well as diuretics, instead of parathyroid hormone. (PTH) replacement.
And in primary hyperparathyroidism, surgical treatment has been recommended as the first line for most patients regardless of phenotype.
Both guidelines were updates to previous ASBMR guidelines on these conditions – 2011 for hypoparathyroidism (although the Endocrine Society published one in 2016) and 2013 for hyperparathyroidism – and emerged from it. an international workshop on parathyroid diseases. They are now in preparation for publication, spread over a total of 17 articles summarizing the review of the evidence and the final recommendations.
Workshop Co-Chair Aliya Khan, MD, McMaster University in Hamilton, Ont., Presented key findings on the underactive parathyroid. Although the overall conclusion regarding conventional treatment versus PTH replacement reached only a “suggestion” status, panel members made stronger recommendations.
For example, the effort has identified some benefits for PTH replacement: moderate evidence indicates that it “probably” improves quality of life somewhat and almost certainly allows patients to reduce doses of calcium and calcium supplements. vitamin D of at least 50%.
Another important clinical concern was to identify patients at risk for permanent hypoparathyroidism after total thyroidectomy. Workshop participants determined that measuring PTH in the hours immediately after surgery deserved a “strong” recommendation, based on moderate-quality evidence indicating that few patients with PTH levels greater than 10 pg / mL 12 to 24 hours later would develop permanent hypoparathyroidism. And even for those with lower levels, the risk remains below 50%.
But most of the advice ended up being based on expert opinion, reflecting the many unknowns regarding hypoparathyroidism. The development process included a survey of practicing endocrinologists. Management approaches for particular aspects of hypoparathyroidism, for which at least 70% of respondents said they have used it in at least 70% of their patients, achieved an “unranked” recommendation.
Genetic testing was among the aspects receiving such public approval. In particular, patients with certain clinical and laboratory characteristics, including young age and other endocrine or metabolic abnormalities, may benefit from genomic analyzes, the guideline says.
Other suggestions in hypoparathyroidism included keeping calcium within a normal range (preferably the lower half), especially during pregnancy, and seeking normalization of phosphate, magnesium, and 25- (OH ) D. Replacement of PTH should be considered when conventional treatment fails to achieve these goals.
Details of diagnostic and monitoring tests to be performed were also covered by these recommendations: serum creatinine, calcium, magnesium, phosphate and 25 (OH) D should be checked both initially and at follow-up.
Khan concluded his presentation with a slide describing new drug therapies still in development. These included long-acting PTH analogs, PTH receptor agonists, calcilytic agents and several others. She did not elaborate, citing her time limitation, but told attendees that “the future is very bright.”
The other workshop co-chair, John Bilezikian, MD, of Columbia University in New York City, handled the primary hyperparathyroidism guideline.
Treatment and outcome are the primary concerns for most patients, and on that note, the guideline should be very reassuring, his presentation suggested.
“In the hands of experienced surgeons, surgery results in biochemical cure in 97.8% [of patients] and is a safe procedure, “Bilezikian said, noting that this conclusion was supported by high-quality evidence. Patients undergoing parathyroid ablation can also expect a” significant reduction “in the risk of vertebral fracture to 10 years, he said.
“It is a curable disease,” he said.
Bilezikian noted that over the years, hyperparathyroidism has evolved from a disease of “bones, stones and moans” to a disease defined by biochemistry and imaging, so asymptomatic cases can now be diagnosed and treated.
Indeed, surgery may be recommended for many of the latter cases (although based on clinician investigation, no hard evidence): any patient under the age of 50 or with high blood calcium, occult fractures or low bone mineral density, kidney failure or kidney stones revealed by imaging.
But the bulk of Bilezikian’s presentation, presumably reflecting the final guideline, has focused on issues other than treatment – diagnosis, epidemiology, etiology, and subgroup management – that are just as important to clinicians.
The disease primarily affects women, at rates of 23 per 10,000 compared to 8.5 per 10,000 men, he said, citing the most recent US data. Such numbers are intimately associated with the degree to which people undergo biochemical screening, as it “leads to an increase in incidence each time screening is introduced”. Many of these incidentally discovered cases are initially classified as asymptomatic, although subsequent examination may reveal previously unrecognized symptoms.
The most common subtype of hyperparathyroidism is marked by excess serum calcium, which can occur with elevated PTH or with “abnormally normal intact PTH,” Bilezikian noted. For diagnostic purposes, hypercalcemia should be confirmed by second or third generation tests performed at least 2 weeks apart.
About 10% of cases of primary hyperparathyroidism are genetic in origin, but genomic testing is not required or recommended to diagnose the condition.
However, primary hyperparathyroidism does not necessarily have to involve hypercalcemia. It is of course defined by high PTH (as confirmed by a second test at least 2 weeks later) and can be diagnosed when causes that would make it secondary hyperparathyroidism, such as vitamin D deficiency or drug side effects, have occurred. been ruled out. outside. Surgery is effective for this subtype, and other glandular systems may be involved, more than with the hypercalcemic version.
Once the diagnosis is made, it is necessary to look for its complications, in particular bone and kidney abnormalities. The guideline will recommend performing dual-energy x-ray absorptiometry tests for bone mineral density in the lumbar spine, hip and radius, as well as spinal imaging. Likewise, kidney function should be assessed and stone imaging performed.
Although many other complications can arise – gastrointestinal, neuropsychiatric, cardiovascular and metabolic – they are “unconventional” and should not be systematically evaluated or taken into account when considering surgical treatment, Bilezikian said. .
For patients refusing or contraindicated for surgery, there are medical options. These include bisphosphonates to reduce fractures, as well as vitamin D supplementation and cinacalcet (Sensipar).
As with hypoparathyroidism, pregnancy is a special case. In these cases, bisphosphonates as well as denosumab (Prolia) should be avoided and cinacalcet is little known. Surgery is best performed during the second trimester, when serum calcium exceeds 11 mg / dL. If you wait until delivery is chosen, newborns should be watched closely for hypocalcemia and surgery should be done before the patient becomes pregnant again, Bilezikian said.
Finally, he presented an extensive research agenda, as the new hyperparathyroidism guideline was also heavily dependent on clinician investigation for its details.
The development of the guideline was supported by grants from Amolyt, Ascendis, Calcilytix and Takeda.
Khan has reported relationships with many pharmaceutical companies. Bilezikian said he had no relevant financial interest.