Calcium is one of the most tightly regulated substances in the human body. It’s essential for bone strength, muscle contraction, nerve signaling, blood clotting, and countless cellular processes. The body maintains blood calcium within a remarkably narrow range — even small deviations can cause serious problems. This precise regulation is controlled primarily by the parathyroid glands, four tiny structures nestled behind the thyroid gland in the neck.

In hyperparathyroidism, one or more parathyroid glands become overactive, producing excessive parathyroid hormone (PTH). This hormone’s primary job is to raise blood calcium levels — and when produced in excess, it does exactly that, but at a cost. PTH pulls calcium from bones, increases calcium absorption from the gut, and reduces calcium excretion by the kidneys. The result is elevated blood calcium (hypercalcemia) accompanied by progressive bone loss, kidney damage, and a constellation of symptoms affecting nearly every organ system.

Primary hyperparathyroidism is surprisingly common, affecting approximately 1 in 500 to 1 in 1,000 adults. It’s the third most common endocrine disorder after diabetes and thyroid disease. Most cases today are discovered incidentally — a routine metabolic panel shows elevated calcium, prompting further investigation that reveals the underlying parathyroid problem. This is actually good news: it means the condition is often caught before severe complications develop.

The classic teaching about hyperparathyroidism describes “bones, stones, abdominal groans, and psychic moans” — referring to osteoporosis, kidney stones, gastrointestinal symptoms, and neuropsychiatric manifestations. While this memorable phrase captures the range of potential complications, many patients today present with milder, less dramatic symptoms or are entirely asymptomatic at diagnosis. However, “asymptomatic” doesn’t mean “harmless” — even without obvious symptoms, the disease may be silently weakening bones and damaging kidneys.

From a prevention perspective, hyperparathyroidism is highly significant. Routine calcium measurement on basic metabolic panels enables early detection. When diagnosed before complications occur, treatment (usually surgical removal of the abnormal parathyroid gland) is curative in over 95% of cases. Even in those who don’t undergo surgery, monitoring and medical management can prevent or slow progression. The key is recognizing elevated calcium as a warning sign that deserves investigation, not dismissal.

This guide provides a comprehensive overview of hyperparathyroidism — from the physiology of calcium regulation to the causes of parathyroid overactivity, from recognizing symptoms to interpreting blood tests, and from treatment options to long-term outcomes. Understanding this condition empowers you to take action when elevated calcium appears on your lab results.

Quick Summary:

• Hyperparathyroidism affects ~1 in 500-1,000 adults — third most common endocrine disorder
• Women are 2-3x more likely to be affected than men
• Primary hyperparathyroidism: Parathyroid gland problem (adenoma, hyperplasia, rarely cancer)
• Secondary hyperparathyroidism: Response to low calcium (usually from kidney disease or vitamin D deficiency)
• Key lab finding: Elevated calcium with elevated or inappropriately normal PTH
• Classic complications: “Bones, stones, abdominal groans, psychic moans”
• Bones: Osteoporosis, fractures, bone pain
• Stones: Kidney stones (calcium-containing)
• Abdominal groans: Constipation, nausea, pancreatitis
• Psychic moans: Depression, fatigue, cognitive difficulties, anxiety
• Often discovered incidentally on routine blood work
• Surgery is curative in >95% of primary cases
• Monitoring is appropriate for some asymptomatic patients
• Early detection prevents osteoporotic fractures and kidney damage

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Understanding Calcium Regulation

The Parathyroid Glands

Despite their name, the parathyroid glands have nothing to do with thyroid function — they just happen to be located near the thyroid. Most people have four parathyroid glands, each about the size of a grain of rice, located on the back surface of the thyroid gland. Some people have fewer or more glands, and the location can vary.

The parathyroid glands have one job: produce parathyroid hormone (PTH) in response to low blood calcium. When calcium levels drop even slightly, the parathyroid glands sense this and release PTH to bring calcium back up. When calcium levels are adequate, PTH secretion decreases. This feedback loop normally maintains calcium within a very narrow range.

How PTH Raises Calcium

PTH raises blood calcium through three main mechanisms:

1. Bone resorption: PTH stimulates osteoclasts (bone-resorbing cells) to break down bone and release calcium and phosphorus into the blood. This is the fastest way to raise calcium but comes at the cost of bone loss if sustained.

2. Kidney effects: PTH acts on the kidneys to:

• Increase calcium reabsorption (reducing calcium loss in urine)
• Decrease phosphorus reabsorption (increasing phosphorus excretion)
• Stimulate conversion of vitamin D to its active form (calcitriol)

3. Intestinal absorption: Through its effect on vitamin D activation, PTH indirectly increases calcium absorption from the gut.

The Role of Vitamin D

Vitamin D works closely with PTH in calcium regulation. Active vitamin D (calcitriol) increases calcium absorption from the intestines — this is its primary role in calcium homeostasis. PTH stimulates the kidney enzyme that converts inactive vitamin D to active vitamin D. This PTH-vitamin D interaction means that vitamin D deficiency can contribute to parathyroid problems, and vitamin D status is always assessed when evaluating calcium disorders.

Normal vs. Abnormal Calcium Regulation

Scenario	Calcium	PTH Response	Outcome
Normal regulation	Low	Increases appropriately	Calcium normalizes
Normal regulation	High	Decreases (suppressed)	Calcium normalizes
Primary hyperparathyroidism	High	Elevated or inappropriately normal	Calcium stays high
Secondary hyperparathyroidism	Low or normal	Elevated (appropriate response)	Trying to raise calcium

The key diagnostic insight: in primary hyperparathyroidism, PTH is elevated when it should be suppressed. The parathyroid gland is ignoring the feedback signal from high calcium and continuing to produce PTH autonomously.

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Types of Hyperparathyroidism

Primary Hyperparathyroidism

Primary hyperparathyroidism occurs when one or more parathyroid glands develop a problem that causes autonomous, unregulated PTH production. The gland produces PTH regardless of blood calcium levels, breaking the normal feedback loop.

Causes of primary hyperparathyroidism:

Single parathyroid adenoma (80-85% of cases): A benign tumor develops in one parathyroid gland, producing excess PTH. The other three glands are normal (and often suppressed). Surgical removal of the adenoma is curative.

Parathyroid hyperplasia (10-15% of cases): All four parathyroid glands become enlarged and overactive. This can occur sporadically or as part of genetic syndromes (MEN1, MEN2A). Treatment usually involves removing 3.5 glands (subtotal parathyroidectomy) or all four glands with reimplantation of a small piece.

Parathyroid carcinoma (<1% of cases): Rare but important to recognize. Usually causes more severe hypercalcemia. Treatment requires complete surgical excision; may recur.

Multiple adenomas (2-5% of cases): Two or more adenomas in different glands.

Secondary Hyperparathyroidism

Secondary hyperparathyroidism is a physiologically appropriate response to low calcium or vitamin D deficiency. The parathyroid glands are working correctly — they’re responding to a signal indicating more PTH is needed. The problem lies elsewhere.

Common causes:

Chronic kidney disease: The most common cause. Failing kidneys cannot activate vitamin D or excrete phosphorus, leading to low calcium and high phosphorus. PTH rises in response. This is nearly universal in advanced CKD and contributes to bone disease (renal osteodystrophy).

Vitamin D deficiency: Without adequate vitamin D, calcium absorption from the gut is impaired. PTH rises to maintain calcium through bone resorption — a compensatory mechanism that works in the short term but causes bone loss if sustained.

Calcium deficiency: Inadequate dietary calcium (rare as a sole cause in developed countries).

Malabsorption: Conditions that impair calcium or vitamin D absorption (celiac disease, gastric bypass surgery, inflammatory bowel disease).

In secondary hyperparathyroidism, calcium is typically low or normal (not elevated), and the treatment is addressing the underlying cause (treating kidney disease, repleting vitamin D).

Tertiary Hyperparathyroidism

Tertiary hyperparathyroidism occurs when long-standing secondary hyperparathyroidism leads to autonomous parathyroid function. After years of stimulation (usually in chronic kidney disease), the parathyroid glands become hyperplastic and begin producing PTH independently, even after the original stimulus is corrected (such as after kidney transplantation). Calcium becomes elevated. Treatment may require surgery.

Normocalcemic Primary Hyperparathyroidism

A recognized variant where PTH is persistently elevated but calcium remains in the normal range (after excluding secondary causes). This may represent early primary hyperparathyroidism before calcium rises, or a distinct entity. Important considerations:

• Must exclude vitamin D deficiency and other causes of secondary hyperparathyroidism first
• PTH elevation must be persistent (confirmed on multiple measurements)
• Some patients progress to hypercalcemic primary hyperparathyroidism over time
• Some may have subtle complications (bone loss, kidney stones) despite normal calcium
• Management is evolving; monitoring for progression is typical
• Surgery may be considered if complications develop

Genetic and Familial Forms

While most primary hyperparathyroidism is sporadic, several genetic syndromes include hyperparathyroidism:

Multiple Endocrine Neoplasia Type 1 (MEN1):

• Autosomal dominant syndrome caused by mutations in the MEN1 gene
• Classic triad: parathyroid tumors (>90%), pituitary tumors, pancreatic neuroendocrine tumors
• Hyperparathyroidism is usually the first manifestation, often appearing in the 20s-30s
• Typically involves multiple glands (hyperplasia or multiple adenomas)
• Surgery is more complex; recurrence is more common
• Family screening is essential

Multiple Endocrine Neoplasia Type 2A (MEN2A):

• Caused by mutations in the RET proto-oncogene
• Primary features: medullary thyroid cancer, pheochromocytoma
• Hyperparathyroidism occurs in 20-30% of cases
• Usually milder than MEN1-associated hyperparathyroidism

Familial Hypocalciuric Hypercalcemia (FHH):

• Autosomal dominant condition caused by inactivating mutations in the calcium-sensing receptor
• The calcium-sensing receptor normally tells the parathyroids to reduce PTH when calcium is high — when this receptor is abnormal, the set point is shifted upward
• Results in mild hypercalcemia with inappropriately normal or slightly elevated PTH
• Critical distinction: FHH is benign and does NOT require surgery. Parathyroidectomy does not correct the hypercalcemia because the problem is in the calcium-sensing mechanism, not the parathyroid glands
• Distinguished from primary hyperparathyroidism by low urinary calcium excretion (calcium-creatinine clearance ratio <0.01)
• Family history of hypercalcemia is common

When to suspect a genetic syndrome:

• Young age at diagnosis (under 40-45)
• Family history of hyperparathyroidism
• Multiple gland involvement
• Associated conditions (pituitary tumors, pancreatic tumors, medullary thyroid cancer, pheochromocytoma)
• Recurrence after surgery

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Who Gets Primary Hyperparathyroidism?

Epidemiology

Primary hyperparathyroidism is common:

• Affects approximately 1 in 500 to 1 in 1,000 adults
• Incidence has increased since routine calcium testing became standard
• Third most common endocrine disorder (after diabetes and thyroid disease)
• Peak incidence in the 50s-60s, but can occur at any age

Risk Factors

Sex: Women are 2-3 times more likely to develop primary hyperparathyroidism than men. The reason isn’t entirely clear but may relate to hormonal factors.

Age: Risk increases with age, particularly after age 50. The condition is uncommon in young adults (and when it occurs in younger patients, genetic syndromes should be considered).

Radiation exposure: Head and neck radiation (for childhood cancers or other conditions) increases parathyroid adenoma risk decades later.

Lithium use: Long-term lithium therapy (for bipolar disorder) increases the risk of both hyperparathyroidism and hypercalcemia.

Genetic syndromes:

• MEN1 (Multiple Endocrine Neoplasia type 1): Parathyroid hyperplasia is the most common manifestation, occurring in over 90% of affected individuals
• MEN2A: Hyperparathyroidism occurs in 20-30%
• Familial hypocalciuric hypercalcemia (FHH): A benign genetic condition that mimics hyperparathyroidism — important to distinguish because surgery is not indicated
• Familial isolated hyperparathyroidism

Family history: Having a first-degree relative with primary hyperparathyroidism increases risk, even without a known genetic syndrome.

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Symptoms and Clinical Features

The clinical presentation of hyperparathyroidism has evolved dramatically. In the past, patients presented with severe complications — dramatic bone disease, multiple kidney stones, profound muscle weakness. Today, most cases are discovered incidentally through routine blood work, often in patients with few or no obvious symptoms.

The Classic Description: “Bones, Stones, Abdominal Groans, and Psychic Moans”

This memorable phrase captures the range of potential manifestations:

Bones: Skeletal Effects

• Osteoporosis: The most common skeletal manifestation today. PTH-driven bone resorption leads to bone loss, particularly at cortical sites (hip, distal radius). Bone mineral density is typically reduced.
• Fractures: Risk of vertebral and non-vertebral fractures is increased, even with “mild” hyperparathyroidism.
• Bone pain: Less common today but can occur with significant bone involvement.
• Osteitis fibrosa cystica: Classic but now rare severe bone disease with bone cysts, brown tumors, and pathological fractures. Seen in severe, prolonged untreated cases.

Stones: Kidney Manifestations

• Kidney stones: Calcium-containing stones (calcium oxalate or calcium phosphate) occur in 15-20% of patients with primary hyperparathyroidism. Hypercalciuria (excess calcium in urine) promotes stone formation.
• Nephrocalcinosis: Calcium deposits in the kidney tissue itself.
• Chronic kidney disease: Prolonged hypercalcemia and/or recurrent stones can damage kidneys, causing or worsening CKD.
• Reduced kidney function: Even without stones, kidney function may decline.

Abdominal Groans: Gastrointestinal Symptoms

• Constipation: Common; hypercalcemia slows gut motility.
• Nausea and poor appetite: Especially with higher calcium levels.
• Abdominal pain: Can occur, sometimes vague.
• Pancreatitis: Associated with hyperparathyroidism, though the mechanism isn’t entirely clear. Risk is higher with significantly elevated calcium.
• Peptic ulcer disease: Historically associated; relationship may be partly due to associated MEN1 syndrome.

Psychic Moans: Neuropsychiatric Manifestations

• Fatigue: Very common and often the most bothersome symptom. May be subtle and attributed to aging or other causes.
• Depression: Increased prevalence in hyperparathyroidism.
• Cognitive difficulties: “Brain fog,” poor concentration, memory problems.
• Anxiety: More common than in the general population.
• Sleep disturbances: Insomnia, poor sleep quality.
• Weakness: Generalized muscle weakness, particularly proximal muscles.

The “Asymptomatic” Patient

Many patients discovered through routine blood work report no symptoms — or so they think. This phenomenon deserves careful consideration:

• Symptoms may be subtle: Fatigue and cognitive changes are often dismissed as aging, stress, menopause, or normal variation. Patients may not realize these are symptoms until they resolve after treatment.
• Adaptation: Symptoms that develop slowly over years may be accepted as “normal” — patients forget what feeling well feels like.
• Symptoms may only be recognized after treatment: Many “asymptomatic” patients feel dramatically better after parathyroidectomy — they didn’t realize they were symptomatic until their symptoms resolved. This is one of the most striking aspects of treating hyperparathyroidism.
• Silent organ damage may be occurring: Bone loss and kidney damage can progress without obvious symptoms. By the time a fracture or kidney stone occurs, significant damage has already happened.
• True absence of symptoms is possible: Some patients genuinely have no symptoms or end-organ effects and may be appropriate for monitoring rather than surgery. But this should be a diagnosis of exclusion after careful assessment.

Symptoms by Calcium Level

The severity of symptoms often correlates with the degree of hypercalcemia:

Mild hypercalcemia (slightly above normal):

• May be asymptomatic or have subtle symptoms
• Fatigue, mild cognitive changes
• Often discovered incidentally

Moderate hypercalcemia:

• More pronounced symptoms
• Increased thirst and urination (polyuria, polydipsia)
• Constipation
• Muscle weakness
• Cognitive difficulties more apparent

Severe hypercalcemia (hypercalcemic crisis):

• Medical emergency
• Severe dehydration
• Confusion, lethargy, potentially coma
• Cardiac arrhythmias
• Nausea, vomiting
• Requires urgent treatment

Severe hypercalcemia is more commonly associated with malignancy than with primary hyperparathyroidism, but parathyroid carcinoma and parathyroid crisis can cause extreme calcium elevations.

Cardiovascular Effects

Hyperparathyroidism has been associated with cardiovascular abnormalities:

• Hypertension (though the relationship is complex)
• Left ventricular hypertrophy
• Vascular calcification
• Possible increased cardiovascular mortality (data are mixed)

Whether parathyroidectomy improves cardiovascular outcomes remains under study.

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Effects on Blood Work

Laboratory testing is central to diagnosing and managing hyperparathyroidism. Understanding the expected patterns helps with interpretation.

Calcium

Serum calcium: Elevated in primary hyperparathyroidism. This is typically the first abnormality detected. Calcium may be persistently elevated or intermittently elevated early in the disease.

Ionized calcium: The biologically active form (not bound to proteins). More accurate than total calcium, especially when protein levels are abnormal. Elevated in hyperparathyroidism.

Albumin-corrected calcium: Total calcium should be corrected for albumin levels — low albumin can make total calcium appear falsely normal when ionized calcium is actually elevated.

Parathyroid Hormone (PTH)

The key diagnostic test. In primary hyperparathyroidism:

• Parathyroid Hormone (PTH) is elevated in ~85% of cases
• PTH is “inappropriately normal” (in the upper normal range) in ~15% — this is still abnormal because PTH should be suppressed when calcium is high
• PTH is rarely truly low in primary hyperparathyroidism

The critical insight: Finding elevated calcium with elevated or non-suppressed PTH is the biochemical diagnosis of primary hyperparathyroidism. Other causes of high calcium (malignancy, vitamin D toxicity, etc.) suppress PTH.

Phosphorus

Typically low or low-normal in primary hyperparathyroidism. PTH increases kidney phosphorus excretion. This helps distinguish from other causes of hypercalcemia.

Vitamin D

25-hydroxyvitamin D: Should always be measured. Vitamin D deficiency is common and can coexist with or mask primary hyperparathyroidism. Deficiency should be corrected (which may unmask or worsen hypercalcemia).

1,25-dihydroxyvitamin D (calcitriol): The active form. Often elevated in primary hyperparathyroidism (PTH stimulates its production). Not routinely measured but can be helpful in complex cases.

24-Hour Urine Calcium

Essential to distinguish primary hyperparathyroidism from familial hypocalciuric hypercalcemia (FHH):

• Primary hyperparathyroidism: Urine calcium is typically normal or elevated
• FHH: Urine calcium is low (calcium-creatinine clearance ratio <0.01)

This distinction is critical because FHH is benign and does not require surgery, while primary hyperparathyroidism often does.

Kidney Function

Creatinine and GFR should be assessed. Elevated creatinine may indicate kidney damage from hypercalcemia or stones.

Bone Turnover Markers

May be elevated, reflecting increased bone resorption. Not routinely needed for diagnosis but sometimes helpful.

Diagnostic Pattern Summary

Test	Primary Hyperparathyroidism	Secondary Hyperparathyroidism	Malignancy-Related Hypercalcemia
Calcium	Elevated	Low or normal	Elevated (often markedly)
PTH	Elevated or inappropriately normal	Elevated (appropriate)	Suppressed (low)
Phosphorus	Low or low-normal	High (in CKD)	Variable
Vitamin D	Variable; calcitriol often high	Often low (causative)	Variable

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Diagnosis

When to Suspect Hyperparathyroidism

Consider testing for hyperparathyroidism when:

• Elevated calcium is found on routine blood work (most common scenario)
• Recurrent kidney stones, especially calcium-containing stones
• Osteoporosis or fragility fracture, especially in unexpected patients
• Family history of hyperparathyroidism or MEN syndromes
• Symptoms suggestive of hypercalcemia (fatigue, cognitive changes, constipation, polyuria)
• Unexplained chronic kidney disease

Diagnostic Workup

Step 1 — Confirm hypercalcemia: Repeat calcium measurement (at least twice) to confirm it’s persistently elevated, not a lab error or transient finding. Check albumin or obtain ionized calcium.

Step 2 — Measure PTH: This is the key test. Elevated or inappropriately normal PTH with high calcium = primary hyperparathyroidism.

Step 3 — Measure vitamin D: 25-hydroxyvitamin D to assess vitamin D status.

Step 4 — 24-hour urine calcium: To rule out FHH and assess kidney calcium handling.

Step 5 — Assess for complications:

• Kidney function (creatinine, GFR)
• Bone density (DXA scan at spine, hip, and distal radius)
• Kidney imaging if history of stones or to check for nephrocalcinosis

Localization Studies

Once primary hyperparathyroidism is biochemically diagnosed, imaging helps locate the abnormal gland(s) before surgery. This is crucial for planning minimally invasive surgery.

Sestamibi scan (parathyroid scintigraphy):

• Nuclear medicine study using technetium-99m sestamibi
• Hyperfunctioning parathyroid tissue takes up and retains the tracer
• Often combined with SPECT (single-photon emission CT) for 3D localization
• Sensitivity: 70-90% for single adenomas; lower for multigland disease
• Particularly useful for identifying ectopic (abnormally located) glands

Neck ultrasound:

• Non-invasive, no radiation, relatively inexpensive
• Can identify parathyroid adenomas as hypoechoic nodules posterior to the thyroid
• Operator-dependent — experience matters
• Normal parathyroid glands are usually not visible (too small)
• Sensitivity: 70-80%
• Also useful for evaluating thyroid nodules (which may coexist)

4D-CT scan:

• High-resolution CT with multiple contrast phases
• Parathyroid adenomas show characteristic enhancement patterns
• Excellent anatomic detail for surgical planning
• Good for detecting adenomas missed by sestamibi and ultrasound
• Higher radiation dose than other modalities
• Often used for reoperative cases or when initial imaging is negative

MRI:

• No radiation exposure
• Useful for identifying ectopic mediastinal glands
• Less commonly used as first-line imaging

Combination approach: Many centers use concordant imaging (sestamibi + ultrasound). When both studies identify the same gland, accuracy is very high. Discordant or negative results may prompt additional imaging or bilateral exploration.

Important principle: Localization studies are for surgical planning, NOT for diagnosis. A negative imaging study does not rule out hyperparathyroidism if the biochemistry is diagnostic. Surgery can still be performed with bilateral exploration. The diagnosis is biochemical; imaging just guides the surgical approach.

Differential Diagnosis of Hypercalcemia

Not all elevated calcium is hyperparathyroidism. Other causes must be considered:

Malignancy:

• Second most common cause of hypercalcemia (after hyperparathyroidism)
• Usually causes more severe hypercalcemia
• Mechanisms: PTHrP secretion (most common), bone metastases, increased calcitriol production (lymphoma)
• Key distinction: PTH is suppressed (low), not elevated

Vitamin D toxicity:

• From excessive supplementation (very high doses over time)
• PTH is suppressed
• 25-hydroxyvitamin D level is very elevated

Granulomatous diseases:

• Sarcoidosis, tuberculosis, fungal infections
• Activated macrophages produce calcitriol independently
• PTH is suppressed

Thiazide diuretics:

• Can cause mild hypercalcemia by reducing urinary calcium excretion
• May unmask underlying primary hyperparathyroidism

Immobilization:

• Prolonged bed rest increases bone resorption
• More significant in patients with high bone turnover (children, Paget’s disease)

Milk-alkite syndrome:

• Excessive calcium and absorbable alkali intake
• Now uncommon

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Treatment

Treatment decisions in primary hyperparathyroidism depend on whether the patient has symptoms, complications, or meets criteria for intervention. The good news is that treatment is highly effective.

Surgery: Parathyroidectomy

Surgical removal of the abnormal parathyroid gland(s) is the only cure for primary hyperparathyroidism. In experienced hands, it is highly successful and safe.

Success rate: >95% cure rate when performed by experienced parathyroid surgeons. Surgeon experience matters significantly — outcomes are better at high-volume centers.

Types of surgery:

• Focused (minimally invasive) parathyroidectomy: When localization studies clearly identify a single adenoma, surgery can target just that gland through a small incision (often under 2 cm). This approach offers quicker recovery, less risk to other structures, can often be done under local anesthesia, and many patients go home the same day.
• Bilateral neck exploration: All four parathyroid glands are identified and examined. Used when localization is unclear, when multiple gland disease is suspected, or in parathyroid hyperplasia. Still highly successful but involves a larger incision and more extensive dissection.

Intraoperative PTH monitoring: A valuable adjunct to surgery. PTH levels are measured during the operation — before and after gland removal. Because PTH has a short half-life (about 4 minutes), levels drop rapidly after successful removal. A significant drop (typically >50%) confirms that the source of excess PTH has been removed. This helps ensure surgical success and can allow a more limited operation.

Potential complications of surgery:

• Hypocalcemia: Temporary low calcium is common after surgery as the remaining parathyroid glands “wake up” after being suppressed. Usually mild and transient.
• Hungry bone syndrome: More significant hypocalcemia can occur when bone rapidly takes up calcium after surgery, especially in patients with significant bone disease. Requires calcium and vitamin D supplementation.
• Recurrent laryngeal nerve injury: The nerve controlling the vocal cord runs near the parathyroid glands. Injury can cause hoarseness. Permanent injury is rare (<1%) with experienced surgeons.
• Permanent hypoparathyroidism: Damage to or removal of all parathyroid tissue. Rare in primary hyperparathyroidism surgery; more of a concern in total thyroidectomy.
• Bleeding, infection: Standard surgical risks; uncommon.

Indications for surgery — current guidelines recommend surgery for patients with:

• Symptomatic disease (kidney stones, fractures, significant symptoms attributable to hypercalcemia)
• Significantly elevated calcium (typically >1.0 above the upper limit of normal)
• Osteoporosis (T-score ≤-2.5 at spine, hip, or distal radius) or vertebral fracture
• Reduced kidney function (eGFR below 60 mL/min)
• Kidney stones or nephrocalcinosis on imaging
• Age under 50 years (longer time for complications to develop)
• 24-hour urine calcium significantly elevated (increased kidney stone risk)
• Evidence of kidney stone formation risk

Surgery for asymptomatic patients: Even patients without clear symptoms may benefit from surgery. Multiple studies show improvements in bone density, quality of life, and possibly cognitive function after parathyroidectomy. The improvement in quality of life is often striking, suggesting that many “asymptomatic” patients actually had subtle symptoms they weren’t aware of. Given the high success rate and low complication rate in experienced hands, many experts now recommend surgery for most patients who are reasonable surgical candidates, rather than waiting for complications to develop.

Monitoring Without Surgery (Observation)

For patients who don’t meet surgical criteria or prefer not to have surgery, active monitoring is appropriate:

Monitoring protocol typically includes:

• Serum calcium annually
• Creatinine/GFR annually
• Bone density every 1-2 years
• Assessment for new symptoms

If monitoring reveals progression (worsening calcium, declining bone density, new stones, reduced kidney function), surgery should be reconsidered.

Medical Management

Medications don’t cure hyperparathyroidism but can manage specific aspects:

Cinacalcet (calcimimetic): Reduces PTH secretion by making the parathyroid glands more sensitive to calcium. Can lower calcium levels but doesn’t improve bone density. Used in patients who cannot have surgery or as a bridge.

Bisphosphonates: Can improve bone density but don’t address the underlying hyperparathyroidism. May be used in patients with osteoporosis who can’t have surgery.

Denosumab: Another bone-protective option.

Vitamin D supplementation: If deficient, vitamin D should be repleted. This may transiently worsen hypercalcemia but is generally safe and appropriate.

Lifestyle Recommendations

• Hydration: Adequate fluid intake helps prevent kidney stones and reduces hypercalcemia effects
• Moderate calcium intake: Neither restrict nor excessively supplement calcium. Moderate dietary calcium is appropriate.
• Avoid dehydration: Can worsen hypercalcemia
• Limit vitamin D supplements to recommended amounts: Avoid mega-doses

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Living with Hyperparathyroidism

After Parathyroidectomy

For most patients, successful surgery is curative and transformative:

Immediate changes:

• Calcium typically normalizes within hours to days
• PTH normalizes
• Some patients notice improved energy and mental clarity within days

Longer-term improvements:

• Bone density typically improves over 1-2 years (sometimes dramatically)
• Kidney stone recurrence risk decreases significantly
• Many patients report feeling “better than they have in years”
• Quality of life improvements are often substantial
• Cognitive symptoms frequently improve
• Mood may improve

Post-operative considerations:

• Hungry bone syndrome: After surgery, bones that were starved for calcium may rapidly take it up, causing temporary hypocalcemia. This is more common when bone disease was significant. Symptoms include tingling, numbness, and muscle cramps. Treatment involves calcium and vitamin D supplementation, sometimes high doses temporarily.
• Temporary hypoparathyroidism: The remaining parathyroid glands may be “stunned” after surgery and take time to resume normal function. Usually resolves within days to weeks.
• Monitoring: Calcium and PTH are typically checked post-operatively, then at 6 months and 1 year, then annually or as needed.
• Persistent or recurrent disease: Occurs in <5% of cases. May indicate missed adenoma, multigland disease, or parathyroid carcinoma. Requires further evaluation and possibly reoperation.

Summary of Outcomes After Successful Surgery

Outcome	Expected Result
Calcium normalization	>95% cure rate
Bone density improvement	Significant gains over 1-2 years
Kidney stone recurrence	Marked reduction
Fatigue/energy	Often dramatic improvement
Cognitive function	Frequently improves
Quality of life	Significant improvement in most patients

Long-Term Monitoring (If Not Having Surgery)

Patients managed without surgery need ongoing surveillance:

• Annual calcium, creatinine, GFR
• Bone density every 1-2 years
• Prompt evaluation if new symptoms develop
• Reconsideration of surgery if disease progresses

Prognosis

The prognosis for primary hyperparathyroidism is excellent with appropriate management:

• Surgery is curative in >95% of cases
• Even without surgery, many patients remain stable with monitoring
• Bone density can improve significantly after treatment
• Kidney stone recurrence decreases
• Quality of life often improves

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Secondary Hyperparathyroidism

Secondary hyperparathyroidism deserves separate consideration as it’s fundamentally different from primary disease.

In Chronic Kidney Disease

This is the most common form of secondary hyperparathyroidism. As kidney function declines:

• Phosphorus excretion decreases, leading to high phosphorus
• Vitamin D activation decreases, impairing calcium absorption
• Calcium levels drop
• PTH rises appropriately to try to maintain calcium

This “CKD-mineral and bone disorder” (CKD-MBD) contributes to bone disease, vascular calcification, and cardiovascular risk. Management involves phosphorus control (diet, phosphate binders), vitamin D supplementation, and sometimes calcimimetics.

In Vitamin D Deficiency

Severe vitamin D deficiency impairs calcium absorption, leading to compensatory PTH elevation. Treatment is simple: vitamin D repletion. PTH typically normalizes as vitamin D is corrected.

Post-Bariatric Surgery

Gastric bypass and other procedures can impair calcium and vitamin D absorption, leading to secondary hyperparathyroidism. Lifelong supplementation and monitoring are required.

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Special Considerations

Hyperparathyroidism During Pregnancy

Hyperparathyroidism during pregnancy poses risks to both mother and fetus:

• Increased risk of miscarriage, preterm labor, and preeclampsia
• Neonatal hypocalcemia can occur (fetus exposed to high calcium suppresses fetal parathyroid glands)
• Mild cases may be managed conservatively with hydration and monitoring
• Severe cases or those with significant hypercalcemia may require surgery
• Surgery is safest in the second trimester if needed
• Calcimimetics (cinacalcet) cross the placenta and are not recommended

Hyperparathyroidism in the Elderly

Special considerations in older patients:

• The condition is more common with advancing age
• Surgical risks must be weighed carefully, but age alone is not a contraindication
• Minimally invasive surgery is well-tolerated by most elderly patients
• The alternative — progressive bone loss and fracture risk — may be more dangerous than surgery
• Medical management with bisphosphonates may be appropriate for those who cannot undergo surgery
• Monitoring is reasonable for mild, stable disease in very elderly or frail patients

Parathyroid Carcinoma

Though rare (<1% of primary hyperparathyroidism), parathyroid carcinoma is important to recognize:

• Usually presents with severe hypercalcemia (often markedly elevated)
• Palpable neck mass may be present
• PTH levels are often very high
• May invade surrounding structures
• Treatment is complete surgical excision
• Prognosis depends on completeness of resection
• Can recur; long-term monitoring is essential
• May require adjuvant treatments if incompletely resected

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Prevention and Early Detection

The Value of Routine Calcium Screening

Most cases of primary hyperparathyroidism today are discovered incidentally through routine blood work. This is valuable:

• Earlier detection means less time for complications to develop
• Patients are diagnosed before severe symptoms occur
• Surgery is often simpler and more successful for smaller adenomas

Don’t Ignore Elevated Calcium

An elevated calcium should never be dismissed without explanation. Even mildly elevated calcium warrants investigation:

• Confirm with repeat testing
• Measure PTH
• Determine the cause

The mindset that “it’s just a little high” delays diagnosis and allows preventable complications.

Family Screening

First-degree relatives of patients with primary hyperparathyroidism should be aware of their increased risk. Periodic calcium screening is reasonable, and genetic testing may be appropriate if a hereditary syndrome is suspected.

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Key Takeaways

Hyperparathyroidism is a common, treatable condition where early detection through routine calcium testing enables intervention before serious complications develop. The key messages:

• Primary hyperparathyroidism is common: Affects 1 in 500-1,000 adults; third most common endocrine disorder
• Most cases are discovered incidentally: Elevated calcium on routine blood work prompts the diagnosis
• The diagnostic pattern: Elevated calcium with elevated or inappropriately normal PTH
• Don’t ignore elevated calcium: Every elevated calcium deserves explanation
• Complications are preventable: Osteoporosis, fractures, and kidney stones can be avoided with early treatment
• Surgery is curative: >95% success rate in experienced hands
• Even “asymptomatic” patients often benefit from surgery: Many feel better after treatment
• Monitoring is appropriate for some: Patients who don’t meet surgical criteria can be safely observed
• Secondary hyperparathyroidism is different: PTH elevation in response to low calcium (from kidney disease or vitamin D deficiency) — treat the underlying cause
• Family members may be at risk: Consider screening first-degree relatives

If you have elevated calcium on blood work, ask your healthcare provider about checking your PTH level. Early diagnosis and treatment of hyperparathyroidism prevents complications and often dramatically improves quality of life.