Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

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asymptomatic with surgical indications or symptomatic

1st line – parathyroidectomy

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asymptomatic with surgical indications or symptomatic
1st line – 

parathyroidectomy

Parathyroidectomy is indicated for all patients with symptomatic hyperparathyroidism.[1][2][30][58]

Parathyroidectomy is recommended in patients with asymptomatic hyperparathyroidism with evidence of subclinical target organ complications such as bone disease (osteoporosis/fractures) or renal involvement (reduced kidney function, occult stones) and in those at risk of disease progression.[1][2][30]

Indications for surgery in asymptomatic patients, according to some authorities, include: age <50 years; serum calcium >0.25 mmol/L (>1 mg/dL) above normal range; calculated creatinine clearance <60 mL/minute; bone mineral density T-score <-2.5 at lumbar spine, total hip, femoral neck, or distal third of radius and/or vertebral fracture by x-ray, computed tomography (CT), magnetic resonance imaging, or vertebral fracture assessment using dual-energy x-ray absorptiometry; urinary calcium >250 mg/day in women or >300 mg/day in men; presence of nephrolithiasis or nephrocalcinosis by x-ray, ultrasound or CT.​[1]​​[2][12]

Pre-operative preparation includes adequate hydration and pre-operative localisation tests. Dietary restriction of calcium is not advised, and pre-operative vitamin D replacement is recommended for patients who are vitamin D deficient. Subjective assessment of voice quality is also recommended pre-operatively.[2]

Parathyroidectomy can often be performed on an outpatient basis with same-day discharge. It generally has morbidity and mortality rates of no more than 1%.​[66] Potential significant complications include bleeding, haematoma, hoarseness from recurrent laryngeal nerve injury, voice change from superior laryngeal nerve injury, pneumothorax, or hypocalcaemia (transient or permanent).

When imaging studies are positive for location of a solitary adenoma (occurring in approximately 85% of patients with PHPT), the patient is a candidate for a minimally-invasive, directed parathyroidectomy.[67] Compared with complete bilateral exploration, a minimally-invasive approach appears to have similar recurrence, persistence, and re-operation rates, but lower overall complication rates and somewhat shorter operative time. The lower rate of complications seen with minimally-invasive surgery primarily relates to a reduced risk of transient postoperative hypocalcaemia and a lower risk of recurrent laryngeal nerve injury due to reduced dissection.[74][66]​ The minimally-invasive procedure may be performed under general or local anesthesia and uses various techniques, including video-assisted, endoscopic, radio-guided, or a focused lateral approach. Intra-operative serum intact PTH serves to inform the operating surgeon that hyperfunctioning tissue has been removed.[75] A decline of >50% from baseline to 5 minutes and 10 minutes post excision suggests adequate removal of hyperfunctioning tissue.[76]

In people with multiple-gland disease (sporadic or familial), complete cervical exploration with identification of all 4 glands and subtotal resection of parathyroid tissue is the surgical approach.[68] It is also the recommended approach when pre-operative imaging is non-localising or discordant, or when intra-operative parathyroid hormone monitoring is not available.[2]

Rarely, the hypercalcaemia of hyperparathyroidism may be severe (>3.5 mmol/L [>14 mg/dL]); for example, in patients with parathyroid carcinoma. These patients require pre-operative medical management for acute severe hypercalcaemia, such as intravenous fluids and furosemide.

If there is suspicion of parathyroid carcinoma during surgery, complete dissection avoiding capsular disruption is recommended and improves the chance of cure. This may involve en bloc resection of adjacent adherent tissue.[2]

Consider – vitamin D supplementation

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ONGOING
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asymptomatic with surgical indications or symptomatic
Consider – 

vitamin D supplementation

Additional treatment recommended for SOME patients in selected patient group

Preoperative vitamin D repletion is advised in the setting of deficiency.[2][1]​ Patients who are vitamin D deficient should continue to receive vitamin D supplementation after apparently successful parathyroidectomy.[2] Specific treatment regimens based on clinical trial data are not available.

Primary options

ergocalciferol: consult specialist for guidance on dose

OR

colecalciferol: consult specialist for guidance on dose

2nd line – monitoring

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asymptomatic with surgical indications or symptomatic
2nd line – 

monitoring

If patients decline surgery or are not surgical candidates, serum calcium, vitamin D, and creatinine clearance should be measured every 12 months and bone density measured every 1 to 2 years.[1]

Patients should avoid medications that increase serum calcium levels (e.g., thiazide diuretics, lithium).

If symptoms of mental status change or lethargy occur, admission for intravenous hydration and a parathyroidectomy should ensue, if possible. A definitive parathyroidectomy can be performed at any point if the patient agrees and is a surgical candidate.

Consider – bisphosphonate

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asymptomatic with surgical indications or symptomatic
Consider – 

bisphosphonate

Additional treatment recommended for SOME patients in selected patient group

Can be considered adjunctively in patients with low bone mineral density (BMD) and increased risk of fracture.[1]​ Bisphosphonates may increase BMD in the lumbar spine at 1 to 2 years and decrease bone turnover, although fracture outcomes are not available.

Primary options

alendronic acid: 10 mg orally once daily; or 70 mg orally once weekly

OR

risedronate sodium: 5 mg orally once daily; or 35 mg orally once weekly

OR

ibandronic acid: 150 mg orally once monthly; or 3 mg intravenously once every 3 months

OR

zoledronic acid: 5 mg intravenously once annually

Consider – cinacalcet

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asymptomatic with surgical indications or symptomatic
Consider – 

cinacalcet

Additional treatment recommended for SOME patients in selected patient group

Cinacalcet has been shown to lower serum calcium and serum intact PTH.[70][71] It is a calcimimetic that modulates the activity of the calcium-sensing receptor, the principal regulator of serum intact PTH secretion. Cinacalcet binds to the transmembrane region of the receptor and induces a conformational change that increases the receptor's sensitivity to calcium. The most common adverse effects, nausea and vomiting, lead to poor tolerance and must be monitored very closely. Resulting volume depletion may worsen hypercalcaemia.

Previously approved for management of difficult-to-treat secondary hyperparathyroidism and inoperable parathyroid carcinoma, it may now be used in selected cases of primary hyperparathyroidism; for example, in those who are symptomatic but not surgical candidates or who decline surgery.[12]

Primary options

cinacalcet: 30 mg orally once daily, increase gradually to 30 mg twice daily until serum calcium levels have normalised

Consider – vitamin D supplementation

Back
ONGOING
|
asymptomatic with surgical indications or symptomatic
Consider – 

vitamin D supplementation

Additional treatment recommended for SOME patients in selected patient group

For patients who decline surgery or who are not surgical candidates, vitamin D replacement is recommended for those who are vitamin D deficient.[12][1]​ Specific treatment regimens based on clinical trial data are not available.

Primary options

ergocalciferol: consult specialist for guidance on dose

OR

colecalciferol: consult specialist for guidance on dose

asymptomatic with no surgical indications

1st line – monitoring

Back
ONGOING
|
asymptomatic with no surgical indications
1st line – 

monitoring

Indications for surgery in asymptomatic patients, according to some authorities, include: age <50 years; serum calcium >1 mg/dL above normal range; calculated creatinine clearance <60 mL/minute; bone mineral density T-score <-2.5 at lumbar spine, total hip, femoral neck, or distal third of radius, and/or vertebral fracture by x-ray, computed tomography (CT), magnetic resonance imaging, or vertebral fracture assessment using dual-energy X-ray absorptiometry; urinary calcium >250 mg/day in women or >300 mg/day in men; presence of nephrolithiasis or nephrocalcinosis by x-ray, ultrasound or CT.​[1][2][12]​​​ Patients without specific indications for surgery may be monitored, but there is some epidemiological evidence to suggest that even mild/asymptomatic primary hyperparathyroidism may be associated with multiple negative outcomes, including overall mortality and cardiovascular disease, that in turn may be linked to high baseline parathyroid hormone concentrations.[79][80]

In patients being monitored, serum calcium, vitamin D, and creatinine clearance should be measured every 12 months and bone density measured every 1 to 2 years.[1]

Patients should avoid medications that increase serum calcium levels (e.g., thiazide diuretics, lithium).

Consider – vitamin D supplementation

Back
ONGOING
|
asymptomatic with no surgical indications
Consider – 

vitamin D supplementation

Additional treatment recommended for SOME patients in selected patient group

For patients who are candidates for monitoring, vitamin D replacement is recommended for those who are vitamin D deficient.[12][1]​ Specific treatment regimens based on clinical trial data are not available.

Primary options

ergocalciferol: consult specialist for guidance on dose

OR

colecalciferol: consult specialist for guidance on dose

2nd line – parathyroidectomy

Back
ONGOING
|
asymptomatic with no surgical indications
2nd line – 

parathyroidectomy

A definitive parathyroidectomy can be performed at any point if symptoms or indications ensue, or if the patient prefers surgery and is a surgical candidate.

Consider – vitamin D supplementation

Back
ONGOING
|
asymptomatic with no surgical indications
Consider – 

vitamin D supplementation

Additional treatment recommended for SOME patients in selected patient group

Preoperative vitamin D repletion is advised in the setting of deficiency.[2][1]​ Patients who are vitamin D deficient should continue to receive vitamin D supplementation after apparently successful parathyroidectomy.[2] Specific treatment regimens based on clinical trial data are not available.

Primary options

ergocalciferol: consult specialist for guidance on dose

OR

colecalciferol: consult specialist for guidance on dose

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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