We attended the ECE2023 in Istanbul virtually this year and were very pleased to see parathyroid conditions so well represented. We report the main sessions below.
In the first Meet the Expert session Professor Heide Siggelkow gave an excellent overview of ADH1 from symptom onset to diagnosis, with case studies called ‘Beyond Hypoparathyroidism: diagnosing and treating ADH1 patients.’ In her summary, she said that ADH1 is a rare genetic disorder causing hypoparathyroidism. Patients present with hypocalcemia, hyperphosphatemia, low or low normal PTH and normal or increased urinary calcium. At diagnosis nephrolithiasis or nephrocalcinosis may be present. Genetic analysis is essential for diagnosis (often today as panel diagnosis). ADH is caused by AD heterozygous activating CASR mutations and its prevalence is estimated to be 3.9 /100.000. Patients with hypoparathyroidism due to ADH1 should be treated carefully with conventional therapy to minimize hypercalciuria and nephrolithiasis and may not treat the underlying disease. She commented that Encaleret is being investigated as a potential treatment option for the ADH1 in adults but is not approved for use by any regulatory authority as its efficacy and safety have not been established.
Next up was an excellent presentation by Dr Stefan Pilz from Austria on ‘Randomized clinical trials with Vitamin D’. 50% of the world population is still vitamin D deficient ie <50nmol/L. The optimal level is 75nmol/L which can be achieved by taking 2000iu daily. Doses of 3,200 to 4000iu appear to increase the risk of hypercalcaemia but rates of kidney stones or hypercalciuria were not significantly affected. He concluded that there would be better results if trials were restricted to those with vitamin deficiency; that apart from bone health vitamin D may improve respiratory infections and the immune system and is beneficial in pregnancy; that daily supplementation is more effective than bolus ( large ) doses; that screening should be done if there is a condition such as osteoporosis, parathyroid etc and vitamin D clinical trials for those on calcium & magnesium should be considered.
The ‘Hypoparathyroidism and Current Treatment Landscape’ session was very informative . In ‘Rethinking the Hypoparathyroidism Treatment Paradigm’ Prof Heide Siggelkow summarised the condition and the current treatment landscape. Dr Christopher Sibley from Transcon in Copenhagen explained how the drug worked and Prof Peter Schwarz outlined the data from the ongoing Transcon PTH clinical trials which is looking very promising.
The’ Bone and Calcium’ session was very interesting.
- Dr Guila del Sindico in Italy presented a ‘Clinical picture of early infancy PTH-resistance syndromes: is it time to improve diagnostic criteria?’ about PTH resistance, looking at PHP and related conditions in children under 2 years old.
- Next came a talk on Eneboparatide, the new PTH and PTHrP analog by Michael Culler from Amolyt Pharma. Early data looks very promising and the clinical trial is recruiting now in the UK.
- From Belgium we heard from Dr Ewout Verly about a useful preliminary study of the ‘Thiazide Challenge Test’ devised to differentiate between primary hyperparathyroidism and secondary hyperparathyroidism due to idiopathic hypercalciuria.
- Daniala Rovito from France spoke about ‘A Vitamin D Receptor antagonist as a potent and safe treatment for Idiopathic Infantile Hypercalcemia’.
- Finally Sabrina Corbetta from Italy presented the results of a large study on ‘Skeletal phenotypes in postmenopausal women with primary hyperparathyroidism (PHPT)’.
There were a huge number of posters and abstract on Primary Hyperparathyroidism. Here are just a few of them:
- Dr Dimitrii Buzanakov and his team from Russia considered long-term quality of life outcomes of parathyroidectomy in patients with primary hyperparathyroidism, from the patient’s perspective. They found that a successful parathyroidectomy was accompanied with remarkable QoL improvement for at least 24 months after surgery in both “symptomatic” and “asymptomatic” PHPT patients. Mental QoL component was the only one factor significantly predicting QoL response after surgery. This finding suggests that patients without overt clinical manifestation or prominent hypercalcemia, but experiencing mental health issues may benefit from the operation.
- One of the most popular posters was this one about locating adenomas in primary hyperparathyroidism patients.
- Diagnosis of primary hyperparathyroidism is another area which was recognised as being difficult. This Turkish study found their ‘New and Valuable Predictor for the Diagnosis of Primary Hyperparathyroidism: Ca/P Ratio‘ to be very successful.
‘Primary hyperparathyroidism (PHPT) is a common endocrine disorder that is characterized by hypercalcemia and elevated or normal levels of parathyroid hormone (PTH). Most PHPT cases are incidentally discovered when routine laboratory analysis reveals hypercalcemia. PHPT should be considered in any person with elevated serum calcium (Ca) levels and no clear evidence of malignancy. Serum phosphorus (P) is low due to the phosphaturic effects of PTH and mostly in the lower half of the normal range. As serum Ca and P are inversely related in PHPT, we examined the diagnostic value of the serum Ca/P ratio in the diagnosis of PHPT. They concluded that Ca/P is a precious predictor for the diagnosis of PHPT and it can be used instead of evaluating serum Ca and P levels solely. As Ca/P ratio is easily accessible and inexpensive, it will be useful for PHPT diagnosis and provide simplicity especially for the practitioners with limited resources.
Finally, in the second Meet the Expert session Dr Bart L Clarke from the USA presented ‘New treatments in Hypopara from lab bench to bedside.’ He gave a brief overview of hypoparathyroidism, summarized management guidelines and explained the new and upcoming treatments. He said that in the next 5-10 years there should be a wealth of options and very interesting biology and science, as part of that, to understand better the functioning of PTH and calcium homeostasis in the body.’
The many abstracts on both hypoparathyroidism and primary hyperparathyroidism studies from this conference may be viewed here. (Key in your chosen condition and submit).
We warmly congratulate Dr Maria Luisa Brandi, winner of the #ECE2023 European Hormone Medal Award. She chose to give her lecture on ‘The Parathyroid Story : a never ending saga.’
Here is the abstract:
”Just before the turning of the 20th century a detailed series of connected events led to the understanding of the physiology, pathophysiology, chemical synthesis, cellular and molecular biology, and pharmacological use of parathyroid hormone (PTH) in the next 120 years. Thanks to scientists like Fuller Albright, Gerald D. Aurbach, John T. Potts, Karen K. Winer, Thomas J. Gardella, and many others, huge progress has been made over the decades through biotechnological advances to increase the medical knowledge regarding PTH. From 2002 the revolutionary pharmacological application of periodic administration of the PTH analog, teriparatide, in the treatment of osteoporosis opened to the development of PTH peptides as drugs to be used in bone and mineral disorders. After this success story a synthetic peptide of human PTH-related protein, abaloparatide, was approved for the treatment of osteoporosis. In 1994, before the development of teriparatide for osteoporosis, the first systematic investigation into synthetic human PTH 1-34 (later indicated as teriparatide) replacement therapy in hypoparathyroidism was launched. Only in 2015 human intact PTH was approved as the first hormone replacement therapy for treating hypoparathyroidism. The challenges ahead for medicinal chemists are to design compounds that affect the PTH receptor in a tissue selective manner. Such developments seem predictable, based on new advances in parathyroid research. “The saga of PTH will continue in the biotechnology of its analogs and the interest of pharmaceutical firms in this field’s potential.”
Finally, we were able to attend online the ESE meeting with affiliated patient groups during the ECE to discuss EDCs, drug shortages and future events. Thank you to the European Society of Endocrinology for the opportunity to participate in the ECE2023 and for setting up the Patient Voice Session to help us be heard. Congratulations to the patient groups who presented there this this year too.
Liz Glenister & Mandy Mainland