European expert consensus on practical management of specific aspects of parathyroid disorders in adults and in pregnancy: recommendations of the ESE Educational Program of Parathyroid Disorders (PARAT 2021)

ESE · 2021 · Europe

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Authors: Jens Bollerslev, Lars Rejnmark, Alexandra Zahn et al.
Title: European expert consensus on practical management of specific aspects of parathyroid disorders in adults and in pregnancy: recommendations of the ESE Educational Program of Parathyroid Disorders (PARAT 2021)
Journal: European Journal of Endocrinology, 2021
DOI: 10.1530/EJE-21-1044
Licence: CC BY 4.0
Changes: Verbatim excerpts; formatting adapted

Full text retrieved 2026-10-27 from Europe PMC · PMC8789028

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Recommendations

Verbatim, with grade of recommendation or strength of consensus where given.

Q9 Which biochemical parameters should be monitored to adjust treatment?

We recommend that phosphate and creatinine concentrations should be measured every 3–6 months, depending on disease control and stability of the patient. Serum magnesium concentrations should be measured at least annually, but more frequently if low. Biochemical markers of bone turnover could be useful in assessing the effect of PTH replacement therapy on bone homeostasis, Table 4.

Q1 What preconception advice should be given to women with PHPT?

We recommend that pregnancy, if possible, should be deferred until curative surgery for PHPT has been performed and calcium levels have been normalized.

Q1 How do we differentially diagnose FHH?

Positive family history is a key feature of FHH, so family testing has a pivotal role.
Historic calcium values are important to exclude progressive hypercalcemia as in PHPT.
PTH concentrations > 2-fold above ULN are suggestive of PHPT.
A CCCR of <0.01 (i.e. an excretion fraction of calcium <1%) is a screening tool for FHH, but the ‘cut-off’ is of limited clinical value due to low diagnostic sensitivity and specificity.
Genetic testing is recommended for all patients with suspected FHH, as identification of a pathogenic mutation will confirm the diagnosis and differentiate between types of FHH.
Negative genetic testing does not exclude FHH, and we recommend ongoing follow-up of mutation-negative patients.

Q2 What is normocalcemic PHPT?

Normocalcemic PHPT is a biochemical signature of persistently (>3 months) increased PTH levels in the setting of consistently normal calcium concentrations.
Normocalcemic PHPT represents a diagnosis of exclusion and can only be considered following a careful evaluation of causes of secondary hyperparathyroidism.

Q3 What are the causes of hyperparathyroidism with normal calcium that should be excluded before considering a diagnosis of normocalcemic PHPT?

Detailed and standardized tests are required before making a positive diagnosis of normocalcemic PHPT, and secondary causes of hyperparathyroidism must be excluded.

Q4 What are the manifestations of normocalcemic PHPT and does it progress to hypercalcemic PHPT?

Normocalcemic PHPT may be an early biochemical manifestation of PHPT.
There are no clear data on the natural history of normocalcemic PHPT.

Q5 What is the definition, prevalence, and causes of recurrent PHPT?

The most widely accepted definition of recurrent PHPT is a demonstration of hypercalcemia, after a period of 6 months, in patients successfully operated by PTX, and where normocalcemia was previously documented.
The true prevalence is unknown but estimated to be between 2.5 and 10%.
The recurrence can be tardive, wherefore long-term follow-up is recommended following successful PTX.

Q6 Do we need to act upon persistent elevations of PTH levels, despite normocalcemia?

PTH should not be routinely measured in normocalcemic individuals following parathyroid surgery.

Q7 What is the optimal work-up of patients with recurrent PHPT?

When evaluating recurrent PHPT, it is mandatory to accurately confirm or refute the diagnosis of PHPT.
If confirmed, an active search for potential underlying etiologies should be considered.

Q8 What is the best surgical approach in patients with recurrent PHPT?

A thorough preoperative work-up is imperative, and repeat surgery should only be performed in highly experienced centers.
Depending on the results and etiology, bilateral neck exploration or a focused minimal-invasive PTX should be performed.

Q9 What is the risk and prevention of hypoparathyroidism following surgery for recurrent PHPT?

In the reoperative setting, the risk of transient hypoparathyroidism can be as high as 80%, while the rate of chronic HypoPT is 3–13%.

Q10 Why and when should calcium levels be measured after PTX?

Calcium levels should be measured postoperatively, in parallel to evaluation for symptoms of low calcium concentrations.
To define cure of PHPT after PTX, normocalcemia should last a minimum of 6 months.

Q11 What preoperative advice should be offered to patients awaiting PTX?

Low 25(OH)D levels should be repleted.
Patients should stay well-hydrated.
Hypercalcemic crises require parenteral hydration and may benefit from further medical management; surgery might be prioritized in selected cases after medical stabilization.

Q12 What causes hypocalcemia after PTX?

Postoperative hypocalcemia can be related to hypoparathyroidism (inappropriate low PTH in relation to calcium concentration), accompanied by a high phosphate concentration.
HBS: Massive transfer of calcium to bone – is characterized by normal or high PTH, low phosphate, and magnesium.

Q13 What is optimal follow-up after (successful) PTX?

Genetic testing in young patients (<30 years) and multiglandular disease at any age.
Special cases (parathyroid cancer, syndromic forms) should be followed with a personalized plan in a specialized endocrine unit.
Patients with concomitant osteoporosis are in need of individualized management.

Q1 How do we define chronic postsurgical HypoPT?

Postsurgical HypoPT is suspected in patients with symptomatic or asymptomatic hypocalcemia and low or inappropriately ‘normal’ PTH concentrations.
Chronic postsurgical HypoPT is diagnosed 6 months after anterior neck surgery, if medication is still necessary to maintain calcium concentrations in the lower normal range.

Q2 How can postoperative hypoparathyroidism be prevented?

We recommend that anterior neck surgery is performed only by experienced surgeons, in particular, in patients at risk of postsurgical hypoparathyroidism.
When immediate postsurgical hypoparathyroidism is diagnosed, we recommend a close and coordinated follow-up team including the surgeon, the endocrinologist, and the general practitioner.

Q3 How can parathyroid gland injury be predicted?

We recommend early postoperative PTH monitoring (rather than isolated calcium assessments) to identify patients at risk of post-surgical parathyroid deficiency.

Q4 What is the management of acute hypocalcemia following anterior neck surgery?

The emergency treatment of acute symptomatic hypocalcemia (defined by calcium levels <1.8 mmol/L (<7.21 mg/dL), or ionized calcium <0.9 mmol/L (<3.61 mg/dL) with clinical symptoms and/or ECG signs) consists of the i.v. administration of 200–300 mg (5–7.5 mmol) of elemental calcium by slow i.v. injection, that is 2–3 ampules of 10 mL of 10% calcium gluconate.
Mild postsurgical hypocalcemia should be treated with oral calcium supplements and active vitamin D analogs.

Q5 What is the first-line treatment of chronic HypoPT?

We recommend as first-line treatment of chronic HypoPT active vitamin D analogs (alfacalcidol or calcitriol), combined, when necessary, with oral calcium supplements (mostly calcium carbonate) in divided dosages.
The goal of treatment is to maintain calcium concentrations in the lower part or slightly below the lower limit of the reference range with patients being free of symptoms. Some patients may, however, need higher calcium concentrations to be symptom-free.

Q6 In which patients should second-line therapies be considered?

The conventional treatment does not fully replace PTH actions and therefore does not permit obtaining acceptable disease control in all patients.
We recommend considering second-line treatments (hormone substitution) in patients with inadequate calcemic control, with hypercalciuria, renal stones, nephrocalcinosis, or reduced renal function, with hyperphosphataemia and/or increased calcium–phosphate product, with gastrointestinal tract disorder with malabsorption, with excessive doses of calcium supplementation and/or active vitamin D analogs, and with significantly reduced QoL.

Q7 What are the treatment options for chronic HypoPT refractory to conventional treatment?

We recommend adjunction of thiazide diuretics to the conventional therapy to reduce urinary calcium excretion in patients with hypercalciuria.
Substitution therapy with rhPTH(1–84), or, if unavailable, with rhPTH(1–34), may be considered in patients with hypocalcemia despite optimized conventional therapy, in patients with malabsorption, and with significantly reduced QoL. However, long-term consequences of PTH replacement therapy on the kidney and bone warrant further investigations.

Q8 How to evaluate patient’s symptoms and QoL?

Three disease-specific patient-reported outcome measures are available for HypoPT: the Hypoparathyroid Patient Questionnaire (HPQ 28), the HypoPT Symptom Diary (HSD), and the Hypoparathyroidism Patient Experience Scale Symptom and Impact (HPES-Symptom, HPES-Impact). They represent a valuable tool to evaluate the fluctuations of calcium homeostasis over time but necessitate a broader validation both as research and clinical tools.

Q9 Which biochemical parameters should be monitored to adjust treatment?

We recommend measuring free-ionized or albumin-adjusted calcium concentrations every 3–6 months, and more frequent monitoring in patients requiring treatment adjustment or during intercurrent illness.
We recommend phosphate monitoring every 3–6 months and strongly suggest calcium–phosphate product calculation at every check.
We recommend monitoring renal function with creatinine measurement at every check.
Magnesium concentrations should be measured at least annually and at every check in patients with hypomagnesemia.
Measuring 24-h urinary calcium and creatinine excretions are important to identify patients at risk of developing kidney stones and/or nephrocalcinosis and should be performed every 6–12 months. Urinary calcium/creatinine ratio calculated from fasting morning spot urine is an alternative.

Q10 Which imaging techniques are useful to monitor treatment or to evaluate tissue complications of chronic HypoPT?

We recommend surveillance by renal imaging every 1–2 years to detect nephrolithiasis or nephrocalcinosis. Repeated renal CT scans should be indicated with caution to minimize risk from radiation dosing.
We recommend performing brain CT scans to search for basal ganglia or other brain tissue calcifications in patients with neurologic symptoms including movement disorders, seizures, and neuropsychiatric symptoms.
Whether BMD measurements are helpful in the regular care of patients is questionable.

Q1 (PHPT) – What preconception advice should be given to women with PHPT?

If possible, pregnancy should be deferred until curative surgery for PHPT has been performed.

Q2 (PHPT) – How to treat PHPT during pregnancy?

PTX is preferred. Especially if albumin-adjusted total calcium levels are >2.85 mmol/L (>11.42 mg/dL).
Surgery should be planned in the second trimester.

Q3 (PHPT) – What is the preferred surgical approach for PTX during pregnancy?

In sporadic PHPT, minimally invasive PTX in combination with intraoperative PTH monitoring.
Bilateral neck exploration may be needed in hereditary forms.

Q4 (PHPT) – Which parathyroid imaging modalities should be used in pregnant women with PHPT and indication for surgery?

Two different imaging methods should be aimed for, preferably ultrasonography in combination with either 99mTc-MIBI scan or 4D-dynamic contrast-enhanced MRI, but 18F-Fluorcholine PET/CT or methionine PET/CT may also be considered in selected cases.

Q5 (PHPT) – What are important considerations for the postpartum and lactation period for the mothers with PHPT and their newborns?

Newborns are at an increased risk of hypocalcemia and hypocalcemic seizures.
Ionized calcium levels should be measured in the newborns at least every 2 days starting on day 2 until 1–2 weeks of life.
Consider active vitamin D treatment in case of hypocalcemia in the newborns.
Mothers of newborn babies are at increased risk of maternal hypercalcemic crisis.
During lactation, maternal calcium levels and eGFR should be measured every 4–8 weeks.
PTX should be performed a few weeks after delivery.

Q6 (HypoPT) – What are the treatment targets and surveillance recommendations during pregnancy in women with chronic HypoPT?

Aim to keep calcium levels (ionized or albumin-adjusted) in the lower end of the normal reference interval.
It is difficult to predict precise doses of calcium and active vitamin D needed.
Monitor calcium, phosphorus, eGFR, and magnesium every 3–4 week, and weekly within 1 month before giving birth.
If changes in the doses of calcium and/or active vitamin D are needed, perform monitoring even more frequently.
Maintain circulating 25(OH)D levels in the reference range.

Q7 (HypoPT) – What are the required doses of calcium and active vitamin D during pregnancy in women with chronic HypoPT?

There is a wide variation in the required doses of calcium and active vitamin D during pregnancy.
Dose requirements may change during the course of pregnancy.

Q9 (HypoPT) – How to manage chronic HypoPT during lactation?

Monitoring maternal calcium levels weekly within the first month after delivery and then every 4 weeks.

Q10 (HypoPT) – What are the surveillance and treatment recommendations for newborns of mothers with HypoPT?

Newborns should be monitored clinically with ionized calcium concentrations measured every second day for the first week of life.
Regular native vitamin D supplementation is recommended.

Abstract

This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders in 2019 were discussed during two virtual workshops in 2021 and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosis of familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represents areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborn children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed at a broader clinical audience and were developed with the focus on endocrinologists in training.

Contents of the original publication

The section headings of the original.

Introduction
Methods
Primary hyperparathyroidism
Q1 How do we differentially diagnose FHH?
Q2 What is normocalcemic PHPT?
Q3 What are the causes of hyperparathyroidism with normal calcium that should be excluded before considering a diagnosis of normocalcemic PHPT?
Q4 What are the manifestations of normocalcemic PHPT and does it progress to hypercalcemic PHPT?
Q5 What is the definition, prevalence, and causes of recurrent PHPT?
Q6 Do we need to act upon persistent elevations of PTH levels, despite normocalcemia?
Q7 What is the optimal work-up of patients with recurrent PHPT?
Q8 What is the best surgical approach in patients with recurrent PHPT?
Q9 What is the risk and prevention of hypoparathyroidism following surgery for recurrent PHPT?
Q10 Why and when should calcium levels be measured after PTX?
Q11 What preoperative advice should be offered to patients awaiting PTX?
Q12 What causes hypocalcemia after PTX?
Q13 What is optimal follow-up after (successful) PTX?
Chronic hypoparathyroidism in adults
Q1 How do we define chronic postsurgical HypoPT?
Q2 How can postoperative hypoparathyroidism be prevented?
Q3 How can parathyroid gland injury be predicted?
Q4 What is the management of acute hypocalcemia following anterior neck surgery?
Q5 What is the first-line treatment of chronic HypoPT?
Q6 In which patients should second-line therapies be considered?
Q7 What are the treatment options for chronic HypoPT refractory to conventional treatment?
Q8 How to evaluate patient’s symptoms and QoL?
Q9 Which biochemical parameters should be monitored to adjust treatment?
Q10 Which imaging techniques are useful to monitor treatment or to evaluate tissue complications of chronic HypoPT?
Parathyroid disorders during preconception, pregnancy, and lactation
Management of patients with PHPT in relation to pregnancy?
Management of HypoPT patients in relation to pregnancy
Main statements and recommendations
Primary hyperparathyroidism
Chronic hypoparathyroidism in adults
Parathyroid disorders in relation to pregnancy
Perspectives
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