Global guidelines for the management of hypo- and hyperparathyroidism



Dr Aliya A. Khan

A large international team of experts has developed two comprehensive guidelines for the diagnosis, assessment and management of hypoparathyroidism and hyperparathyroidism, which supersede the guidelines published 5 and 7 years ago.

Aliya A. Khan, MD, presented an overview of the hypoparathyroidism guidelines and John P. Bilezikian, MD, presented key aspects of the hyperparathyroidism guidelines at the 2021 American Society of Bone and Mineral Research (ASBMR).

The guidelines will be published as 17 articles in two issues of the company magazine Journal of Bone and Mineral Research in 2022 – one on hypoparathyroidism and the other on hyperparathyroidism.

The work represents an “unprecedented effort” of more than 100 experts from 16 countries (United States, Canada, Australia, Brazil, China, Denmark, France, Germany, India, Italy, Israel, Lebanon, Singapore, Spain, Sweden and the United Kingdom), Bilezikian said Medscape Medical News in an interview.

More than 100 international and national endocrinology and osteoporosis organizations, societies and patient advocacy groups from more than 50 countries have expressed interest in endorsing the guidelines.

Management of hypoparathyroidism

The new hypoparathyroidism guidelines replace guidelines released in 2016 that were developed at the first international conference on the management of hypoparathyroidism, said Khan, of McMaster University in Hamilton, Ontario, Canada, said declared Medscape Medical News in an email.

There was a need for new hypoparathyroidism guidelines, she explained, due to a better understanding of associated complications, how to predict who will develop postoperative hypoparathyroidism (and how to prevent it), how and when investigate further a genetic cause, when to consider parathyroid hormone (PTH) replacement therapy (and the benefits of the different molecules available today as well as those being evaluated in clinical research), and how to diagnose and manage hypoparathyroidism during pregnancy and breastfeeding.

The hypoparathyroidism experts were divided into four working groups that covered epidemiology and financial burden, etiology and pathophysiology, genetics and diagnosis, and patient assessment and management.

The guidelines, developed over the past 18 months, provide detailed evidence-based recommendations (strong to weak) as well as ungraded recommendations (current practice).

Summarizing some key takeaways, Khan noted that the guidelines recommend for clinicians treating patients with hypoparathyroidism:

  • Diagnose hypoparathyroidism if serum calcium corrected for albumin is low in the presence of low or abnormally normal PTH confirmed twice 2 weeks apart (which may be confirmed by other specified abnormalities).

  • Determine the cause of hypoparathyroidism (which includes postoperative causes, genetic variants, autoimmune causes, radiation, or idiopathic causes).

  • Assess target organ damage.

  • Try to meet treatment goals and minimize the risk of long-term complications.

  • Consider PTH replacement therapy if patients have inadequate control, with symptoms of hypocalcemia or hypercalcemia, high phosphate levels, kidney disease or high urinary calcium, or poor quality of life.

The guideline strongly recommends using PTH measurements after total thyroidectomy to try to predict which patients will develop permanent post-surgical hypoparathyroidism.

It provides a clinical approach to establish the genetic etiology of hypoparathyroidism.

A meta-analysis of 81 studies identified that the most common symptoms / complications of chronic hypoparathyroidism were, in descending order, cataract (24%), infection (18%), nephrolithiasis, renal failure , seizures, depression, ischemic heart disease and arrhythmias.

Based on the best available evidence, the guideline states that “clinicians should carefully determine why a patient has hypoparathyroidism and develop an individualized treatment plan with conventional therapy consisting of calcium, active vitamin D, hydrochlorothiazide and regular vitamin D, ”Khan continued.

“If a patient has poorly controlled hypoparathyroidism with many symptoms or is not doing well, clinicians should consider PTH replacement therapy, as this will replace the missing hormone, reduce calcium loss in the urine, bring back serum calcium at the normal reference range. , and a drop in phosphate (which appears to be associated with calcification of the kidneys and may also contribute to basal ganglia calcification and calcium deposits in the eye), ”she noted.

The guideline also deals with the best way to monitor and treat female patients during pregnancy, childbirth and breastfeeding in order to optimize outcomes for mother and baby. Key points are closer monitoring of patients with normalization of calcium, urinary calcium, phosphate and vitamin D.

Management of primary hyperparathyroidism

Dr John P. Bilezikian

There was a need to update the previous 2014 guidelines developed at the Fourth International Workshop on the Management of Primary Hyperparathyroidism, as, among other things, recent studies provided new evidence on the different clinical phenotypes of primary hyperparathyroidism. and the ways in which the disease affects the skeleton and kidneys, Bilezikian, of the College of Physicians and Surgeons at Columbia University, New York, explained.

The hyperparathyroidism experts were divided into four working groups that covered epidemiology, pathophysiology and genetics; classical and non-classical manifestations of the disease; surgical aspects; and patient assessment and management.

As part of these topics, experts examined biochemical, skeletal and renal outcomes, unclassical features (such as neurocognitive disorders), nutritional and pharmacological approaches, and disease course with or without surgery or medical intervention. .

They made recommendations for the diagnosis of hypercalcemic and normocalcemic phenotypes, differential diagnosis, evaluation of the skeleton and kidney, indications for surgery, the role of parathyroid imaging, indications for pharmacological intervention and monitoring.

“Consider how this disease has seemed to change over the past 50 years,” Bilezikian said. In the 1940s, 1950s and 1960s, patients with hyperparathyroidism were really sick and suffered from severe bone and kidney disease. Then in the 70s, 80s and 90s, the disease was more often discovered thanks to a screening test; elevated serum calcium was a feature of the finding of asymptomatic hyperparathyroidism.

In recent years, hyperparathyroidism is often discovered incidentally, when examining the skeleton or kidneys, he continued.

Primary hyperparathyroidism can now be subdivided into three types: patients who have target organ damage (kidney, bone), patients who do not and patients who have primary normocalcemic hyperparathyroidism.

The guideline covers new drugs that have become available for hyperparathyroidism, as well as surgery (the only cure), including how preoperative imaging can identify the overactive parathyroid gland, and the guidelines detail how to monitor a patient and why a clinician or wouldn’t recommend the surgery, Bilezikian explained.

Ultimately, the treatment is tailored to the individual.

Finally, the guideline identifies eight areas where further research is needed.

The guidelines were funded by unrestricted educational grants from Amolyt, Ascendis, Calcilytix, and Takeda. Khan said he has served on advisory boards for Alexion, Amgen, Amolyt and Takeda, been a consultant for Amgen, received grants from Alexion, Amgen, Takeda and Ascendis, been a researcher for Alexion, Amgen, Takeda, Ascendis and Chugai, and be a speaker for Alexion, Amgen, Takeda and Ultragenyx. Bilezikian did not report any relevant financial relationship.

ASBMR 2021 Annual Meeting. Presented October 3, 2021.

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