Hypoparathyroidism: diagnosis, management and emerging therapies

[helvella]

This forum is, obviously, primarily for thyroid issues. But, as most know, the parathyroid glands are physically adjacent to thyroid tissue. And it is well-known that some thyroid treatments (thyroidectomy and radio-active iodine for two) can result in damage to the parathyroids.

We usually have four parathyroid glands but most claim that we can function adequately with just one functioning gland.

Hence, though we might have many members who have had some parathyroid damage, diagnosed hypoparathyroidism is relatively rarely mentioned.

I suspect that this news (albeit many months after the announcements of approval) kight have passed by many members.

Review Article

Published: 04 February 2025

Hypoparathyroidism: diagnosis, management and emerging therapies

Sarah Khan & Aliya A. Khan

Nature Reviews Endocrinology (2025)

Abstract

Hypoparathyroidism is characterized by inadequate parathyroid hormone (PTH) secretion or action and results in hypocalcaemia, and can lead to hyperphosphataemia and hypercalciuria. Most cases of hypoparathyroidism occur as a complication of surgery, with the remainder due to causes including autoimmune disease, genetic causes, infiltrative diseases, mineral deposition or due to abnormalities in serum levels of magnesium. Hypoparathyroidism can cause multisystem disease, with long-term complications resulting from ectopic calcification as well as renal complications with nephrocalcinosis, nephrolithiasis and renal impairment in addition to respiratory, cardiac or neurological manifestations. Conventional therapy consists of oral calcium salts and active vitamin D but it has limitations, including fluctuations in serum levels of calcium and a high pill burden, and can increase the risk of long-term complications. By contrast, PTH replacement therapy can effectively achieve normal serum levels of calcium, and lower serum levels of phosphate. The long-acting PTH analogue, palopegteriparatide, has been shown to normalize urine levels of calcium. In addition, PTH replacement therapy reduces the pill burden. Palopegteriparatide is also associated with improved quality of life in comparison to conventional therapy. This Review summarizes current recommendations regarding the pathophysiology, evaluation and management of hypoparathyroidism and also references the 2022 international hypoparathyroidism guidelines. Palopegteriparatide has now been approved as PTH replacement therapy for hypoparathyroidism. Emerging therapies will also be presented in this Review.

Key points

● Hypoparathyroidism is a complex disease characterized by inadequate secretion or action of parathyroid hormone (PTH), which leads to hypocalcaemia and can lead to hyperphosphataemia and hypercalciuria.

● Hypoparathyroidism is a biochemical diagnosis based on the confirmation of hypocalcaemia in association with a low or inappropriately normal PTH level.

● The aetiology of hypoparathyroidism can be divided into surgical causes (75–80% of cases) and non-surgical causes (20–25% of cases).

● Hypoparathyroidism affects multiple organ systems, including the renal, skeletal, cardiovascular, ophthalmological and neurological systems.

● Conventional treatment of hypoparathyroidism with oral calcium salts and active vitamin D can cause fluctuating serum levels of calcium and can exacerbate hyperphosphataemia and hypercalciuria. Conventional therapy has not consistently been shown to improve quality of life.

● PTH replacement therapy is now possible with palopegteriparatide, which provides a valuable management option for addressing symptomatic hypocalcaemia and might also reduce the long-term complications of hypoparathyroidism.

nature.com/articles/s41574-...

A Wiki link to Palopegteriparatide:

Palopegteriparatide was approved for medical use in the European Union in November 2023, and in the United States in August 2024.

en.wikipedia.org/wiki/Palop...

MHRA Approves YORVIPATH® (palopegteriparatide) in UK for the Treatment of Adults with Chronic Hypoparathyroidism

parathyroiduk.org/news/mhra...

NICE guideline (in development)

Palopegteriparatide for treating chronic hypoparathyroidism [ID6380]

In development [GID-TA11454] Expected publication date: 16 July 2025

nice.org.uk/guidance/indeve...

[Calceolaria]

Sounds like a godsend. Do GPs know about it I wonder! What is active Vit D?

[helvella Administrator in reply to Calceolaria]

I believe it is calcitriol (1,25-dihydroxycholecalciferol; 1,25(OH)2D).

Wiki link:

en.wikipedia.org/wiki/Calci...

[YorkshireLass_1964]

Thank you for posting this helvella,

I lost a parathyroid on January 2nd during a Hemithyroidectomy this year, it had embedded into the muscle.

I'm having to have a Total Thyroidectomy at the beginning of March follwed by RAI and the consultant said he will try and save my parathyroid's, if this is not possible I can refer to this post for information when discussing my care plan going forward.

It's really appreciated thank you 😊

[helvella Administrator in reply to YorkshireLass_1964]

Here's hoping your parathyroids are saved. All the best.

[birkie in reply to YorkshireLass_1964]

Hi YorkshireLass_1964

Are you aware your parathyroids can be implanted in your arm pit

If they are healthy ?

If they are removed with your thyroid they can be removed from the thyroid tissue an re implanted.

As helvella says you can live quite well with only one para gland , all these tiny glands do is regulate our body's calcium levels which are finally tuned.

I noticed after thyroidectomy your having RAI..are you having full thyroidectomy or partial?

Hope everything go well with your thyroidectomy ❤️

[YorkshireLass_1964 in reply to birkie]

Hello birkie,

Thank you, I was aware you can have them implanted in your armpit, unfortunately my was well and truly embedded and couldn't be separated as successfully as the other parathyroid was.

The RAI will be after the full Thyroidectomy, my left thyroid lobe had a 22 mm papillary carcinoma, histology report confirmed although small it was acting aggressively and has spread into the blood vessels, hence having the follow up TT surgery and RAI, frustrating to say the least as everyone said the chances of the nodule being cancerous were minimal, how wrong they were!

I will update my profile with my journey since being diagnosed in 2019 with Subclinical Hypothyroidism to date, I've a feeling I will need the expertise of this wonderful forum even more going forward 🙏❤️

[pennyannie]

birkie - thought of you immediately I saw this post - hope it is of interest :

[birkie]

Hi helvella❤️

This was mentioned to me by my surgeon before I had my full thyroidectomy in 2019, after removal I was given calcichews , unfortunately for me I'd been diagnosed with primary hyperparathyroidism in 2004 but left with a watch and wait approach 😡

So here's what happened to me...full thyroidectomy in may 2019, given calcichews started on T4 .

In early July 2019 I had the most worst kidney pain ever..[ I knew the pain of kidney stones because I'd passed several [ in hospital and at home] so I recognised the pain immediately, I then vomited, taken to A&E where after several tests [ blood in urine , calcium high] I was told to stop the calcichews immediately.

Unfortunately no one recognised primary hyperparathyroidism 🤦‍♀️ and truthfully I was in to much pain to talk or even think, no parathyroid test was performed with my high calcium 😡.

I had a kidney scan the next day which identified a stone , which passed the technician said I had kidney grit🤷‍♀️ sent back to GP care who did absolutely nothing until my bloods in March 2020 which showed over range pth and calcium , again I got a second diagnosis of primary hyperparathyroidism 🤦‍♀️.

So I didn't fit hypoparathyroid.. in that my parathyroids went overactive not under active after surgery, but any good endocrinologist would have scratched his/ her head wondering why this patients pth had gone over, as they normally see under or paralysed parathyroids after thyroid surgery .

If they'd bothered to look into my history they would have see my diagnosis of primary hyperparathyroidism, I challenged my surgeon on my high calcium when I was able to talk to him, he dismissed it even after I informed him I had primary hyperparathyroidism, my endocrinologist even dismissed it until 2020 when I received the second PHPT diagnosed..by the very endocrinologist who dismissed it first time after my thyroidectomy 😡.

I do despair how little these so called specialist's know very little about the conditions they are trained for😔

[helvella Administrator in reply to birkie]

Thanks for your helpful reply.

It adds to the full story of parathyroids which might help others.