II. Pathophysiology
- Overactive Parathyroid Glands (>=1 of 4 glands)
- Produce excessive Parathyroid Hormone (PTH)
- Results in disorder of bone metabolism
III. Epidemiology
-
Prevalence
- Women: 2-3 cases per 1000 women over age 65 years
- Men: 1 case per 1000 men over age 65 years
- Ages
- Range: 40-70 years old
- Mean: 55 years old
IV. Causes: Primary Hyperparathyroidism
- Single Parathyroid Adenoma (82 to 85%)
- Parathyroid Gland Hyperplasia or hypertrophy (15%)
- Parathyroid Malignancy (rare, accounts for 0.5 to 3% of Primary Hyperparathyroidism)
- Familial Hyperparathyroidism (10-20%): Younger patients
- Multiple Endocrine Neoplasia Type I (MEN I)
- Multiple Endocrine Neoplasia Type I (MEN II)
- Familial Hypocalciuric Hypercalcemia
- Hyperparathyroidism-Jaw Tumor Syndrome
- Neonatal severe Primary Hyperparathyroidism
- Other Parathyroid related causes
- Lithium Therapy
- External neck radiation exposure
- Neck surgery with Parathyroid injury or resection
- Tertiary Hyperparathyroidism
- Accelerated response to chronic Hypocalcemia (in advanced Renal Failure)
- Parathyroid over-produces PTH causing Hypercalcemia
V. Causes: Secondary Hyperparathyroidism
- Vitamin D Deficiency
- Decreased calcium intake
-
Renal Osteodystrophy
- Chronic Kidney Disease stage 4 or stage 5 and
- Decreased 1,25 dihydroxyvitamin D
- Hyperphosphatemia
- Hypocalcemia
- Normocalcemic Hyperparathyroidism (associated with Osteoporosis)
- Diagnosis of exclusion after ruling-out Vitamin D Deficiency and Chronic Kidney Disease
VI. Symptoms
- See Hypercalcemia
- Asymptomatic Hypercalcemia (up to 80% of cases)
VII. Diagnosis
- Mnemonic (classic presentation is uncommon)
- Stones
- Bones
- Abdominal groans
- Psychic moans
- Constellation of findings
- See Hypercalcemia
- Calcium oxalate renal stones (Nephrolithiasis)
- Bony changes
- Osteitis fibrosa
- Salt and pepper skull
- Bone resorption
- Acute Pancreatitis
- Psychosis and depression
VIII. Labs
-
Parathyroid Hormone (PTH) Level elevated
- Measure Intact PTH
- See Parathyroid Hormone for algorithm
- Serum Electrolyte abnormalities
- Hypercalcemia (Use Corrected Serum Calcium)
- Draw Fasting with minimal Occlusion
- Discontinue Thiazide Diuretics for 2 weeks before
- Repeat serum testing in 2 weeks if normal
- Hyperchloremia
- Hypophosphatemia
- Hypokalemia
- Hypercalcemia (Use Corrected Serum Calcium)
- Miscellaneous
- 1,25 Dihydroxyvitamin D3
- Indicated if Serum Calcium low
- 1,25 Dihydroxyvitamin D3
-
Urine Calcium and Phosphate
- Hypercalciuria (24 hour Urine Calcium)
- Hyperphosphaturia
- Arterial Blood Gas
- Renal Function tests
IX. Imaging
- Classic XRay Findings
- Skull XRay
- "Salt and pepper" skull
- Chest XRay
- Distal Clavicle resorption
- Hand XRay
- Second and third middle phalange bone resorption
- Dental XRay
- Bone resorption of Lamina dura around teeth
- Skull XRay
- Sestamibi Technetium Tc 99mParathyroid Scan
- Test Sensitivity for localizing adenoma: 95%
- Causes of non-localizing scan
- Ectopic PTH production
- Diagnostic error
- Four-gland hyperplasia
- End-organ evaluation
X. Differential Diagnosis
- See Hypercalcemia
-
Familial Benign Hypocalciuric Hypercalcemia
- Does not improve with surgery, unlike primary disease
- Calcium to Creatinine ratio <0.01
XI. Management: Medical Monitoring
- Indications
- Asymptomatic patients without surgical indications
- Serum Calcium level only mildly increased
- No priot life-threatening Hypercalcemia
- Normal Renal Function
- Creatinine Clearance >70%
- No Nephrolithiasis
- No Nephrocalcinosis
- Normal Bone Mineral Density (Osteopenia or better)
- Avoid provocative factors
- Thiazide Diuretics and Lithium
- Avoid Volume depletion (maintain hydration)
- Avoid prolonged bedrest or inactivity
- Avoid High Calcium diet
- Avoid Vitamin D supplementation
- Encourage moderate Physical Activity
- Minimize bone resorption
- Encourage 64 ounces non-caffeinated fluid per day
- Minimize risk of Nephrolithiasis
- Encourage moderate calcium intake (1000 mg/day)
- Low Calcium diet may surge Parathyroid Hormone
- Medications
- Calcium Lowering Therapy
- See Hypercalcemia
- Pharmacologic Measures: Reduce bone resorption
- Estrogen Replacement Therapy (Postmenopausal)
- Bisphosphonates
- Calcium Lowering Therapy
XII. Management: Surgery
- Precautions
- Re-evaluate on a periodic basis
- Up to 15% of originally asymptomatic Hyperparathyroidism cases develop a surgical indication within 4.7 years
- Indications in Primary Hyperparathyroidism
- Serum Calcium >12 mg/dl (or >1 mg/dl above the upper limit of normal)
- Hypercalcemic Crisis (Serum Calcium >14 mg/dl)
- 24 hour Urine Calcium >400 mg/day
- Osteoporosis (or T-Score <-2.5 at hip, spine or wrist)
- Osteitis fibrosa cystica
- Nephrolithiasis
- Nephrocalcinosis
- Young patient age (e.g. age <50 years)
- Exacerbating factors
- Dehydration
- Immobile patient
- Creatinine Clearance <60 ml/min/1.73m2 or 30% below age-matched peers
- Persistent Hypercalcemia symptoms (esp neuromuscular)
- Efficacy
- Successful in up to 95% of cases
- Few complications
- Single Parathyroid Adenoma
- Surgery to locate and remove adenoma
- Biopsy a second gland to rule out atrophy
-
Parathyroid hyperplasia or hypertrophy
- Remove 3.5 glands
- Autotransplant tissue into arm muscle
XIII. Monitoring of medically managed patients
- Every 6 month labs
- Every 12 month labs
- Serum Creatinine
- Urinary Calcium Excretion
- Every 6-12 month labs for women
- Bone Density (DEXA Scan)
XIV. References
- Spiegel in Goldman (2000) Cecil Medicine, p. 1402-5
- (1991) Ann Intern Med 114:593-7 [PubMed]
- Bilezikian (2002) J Clin Endocrinol Metab 87:5353-61 [PubMed]
- Taniegra (2004) Am Fam Physician 69(2):333-40 [PubMed]
- Michels (2013) Am Fam Physician 88(4): 249-57 [PubMed]
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Related Studies
Definition (NCI) | Hyperfunction of the parathyroid glands resulting in the overproduction of parathyroid hormone. It may be primary or secondary; primary hyperparathyroidism is caused by parathyroid adenoma, parathyroid hyperplasia, parathyroid carcinoma, and multiple endocrine neoplasia. It is associated with hypercalcemia and hypophosphatemia. Signs and symptoms include weakness, fatigue, nausea, vomiting, constipation, depression, bone pain, osteoporosis, cystic bone lesions, and kidney stones. Secondary hyperparathyroidism is caused by the chronic stimulation of the parathyroid glands in patients with chronic renal failure, rickets, and malabsorption syndromes. |
Definition (NCI_CTCAE) | A disorder characterized by an increase in production of parathyroid hormone by the parathyroid glands. This results in hypercalcemia (abnormally high levels of calcium in the blood). |
Definition (NCI_NCI-GLOSS) | A condition in which the parathyroid gland (one of four pea-sized organs found on the thyroid) makes too much parathyroid hormone. This causes a loss of calcium from the bones and an increased level of calcium in the blood. Symptoms include bone pain and kidney problems. |
Definition (CSP) | abnormally increased activity of the parathyroid glands, which may be primary or secondary; primary hyperparathyroidism is associated with neoplasia or hyperplasia; excess of parathyroid hormone leads to alteration in function of bone, renal tubules, and gastrointestinal mucosa. |
Definition (MSH) | A condition of abnormally elevated output of PARATHYROID HORMONE (or PTH) triggering responses that increase blood CALCIUM. It is characterized by HYPERCALCEMIA and BONE RESORPTION, eventually leading to bone diseases. PRIMARY HYPERPARATHYROIDISM is caused by parathyroid HYPERPLASIA or PARATHYROID NEOPLASMS. SECONDARY HYPERPARATHYROIDISM is increased PTH secretion in response to HYPOCALCEMIA, usually caused by chronic KIDNEY DISEASES. |
Concepts | Disease or Syndrome (T047) |
MSH | D006961 |
ICD9 | 252.00, 252.0 |
ICD10 | E21.3 |
SnomedCT | 190451000, 154696001, 66999008 |
English | Hyperparathyroidism, HYPERPARATHYROIDISM, Hyperparathyroidism, unspecified, hyperparathyroidism (diagnosis), hyperparathyroidism, Hyperparathyroidism NOS, Hyperparathyroidism [Disease/Finding], HPTH - Hyperparathyroidism, Hyperparathyroidism (disorder), hyperfunction; parathyroid, parathyroid; hyperfunction, Hyperparathyroidism, NOS |
French | HYPERPARATHYROIDIE, Hyperparathyroïdie SAI, Hyperparathyroïdie, Hyperparathyroïdisme |
Spanish | HIPERPARATIROIDISMO, Hiperparatiroidismo NEOM, hiperparatiroidismo (trastorno), hiperparatiroidismo, Hiperparatiroidismo |
German | HYPERPARATHYREOIDISMUS, Hyperparathyreoidismus NNB, Hyperparathyreoidismus, nicht naeher bezeichnet, Hyperparathyreoidismus |
Dutch | hyperparathyroïdie NAO, bijschildklier; hyperfunctie, hyperfunctie; bijschildklier, Hyperparathyroïdie, niet gespecificeerd, hyperparathyroïdie, Parathyreotoxicose, Parathyrotoxicose, Hyperparathyreoïdie, Hyperparathyroïdie, Parathyroïdie, hyper- |
Italian | Iperparatiroidismo NAS, Iperparatiroidismo |
Portuguese | Hiperparatiroidismo NE, HIPERPARATIROIDISMO, Hiperparatireoidismo |
Japanese | 副甲状腺機能亢進症NOS, 副甲状腺機能亢進症, フクコウジョウセンキノウコウシンショウ, フクコウジョウセンキノウコウシンショウNOS |
Swedish | Hyperparatyreos |
Czech | hyperparatyreoidismus, Hyperparatyreóza, Hyperparatyreóza NOS |
Finnish | Hyperparatyreoosi |
Russian | GIPERPARATIREOIDIZM, GIPERPARATIREOZ, ГИПЕРПАРАТИРЕОЗ, ГИПЕРПАРАТИРЕОИДИЗМ |
Korean | 상세불명의 부갑상샘 기능항진증 |
Croatian | HIPERPARATIREOIDIZAM |
Polish | Nadczynność przytarczyc |
Hungarian | Hyperparathyreosis k.m.n., Hyperparathyreosis |
Norwegian | Hyperparatyreoidisme, Hyperparatyreose |
Ontology: Hyperparathyroidism, Primary (C0221002)
Definition (NCI) | Hyperfunction of the parathyroid glands resulting in the overproduction of parathyroid hormone. It is caused by parathyroid adenoma, parathyroid hyperplasia, parathyroid carcinoma, and multiple endocrine neoplasia. It is associated with hypercalcemia and hypophosphatemia. Signs and symptoms include weakness, fatigue, nausea, vomiting, constipation, depression, bone pain, osteoporosis, cystic bone lesions, and kidney stones. |
Definition (MSH) | A condition of abnormally elevated output of PARATHYROID HORMONE due to parathyroid HYPERPLASIA or PARATHYROID NEOPLASMS. It is characterized by the combination of HYPERCALCEMIA, phosphaturia, elevated renal 1,25-DIHYDROXYVITAMIN D3 synthesis, and increased BONE RESORPTION. |
Concepts | Disease or Syndrome (T047) |
MSH | D049950 |
ICD9 | 252.01 |
ICD10 | E21.0 |
SnomedCT | 190452007, 36348003 |
English | HYPERPARATHYROIDISM PRIMARY, Hyperparathyroidism primary, Primary hyperparathyroid, Hyperparathyroidism, Primary [Disease/Finding], primary hyperparathyroidism, hyperparathyroidism primary, hyperparathyroidism primary (diagnosis), Primary hyperparathyroidism, Primary hyperparathyroidism (disorder), hyperparathyroidism; primary, primary; hyperparathyroidism, Hyperparathyroidism, Primary, Hyperparathyroidisms, Primary, Primary Hyperparathyroidisms, Primary Hyperparathyroidism |
Dutch | primaire hyperparathyroïdie, hyperparathyroïdie; primair, primair; hyperparathyroïdie, Primaire hyperparathyroïdie, hyperparathyroïdie primair |
German | primaerer Hyperparathyreoidismus, Primaerer Hyperparathyreoidismus, Hyperparathyreoidismus primaer, Hyperparathyreoidismus, primärer, Primärer Hyperparathyreoidismus |
Italian | Iperparatiroidismo primitivo, Iperparatiroidismo primario |
Swedish | Hyperparatyreos, primär |
Japanese | ゲンパツセイフクコウジョウセンキノウコウシンショウ, 原発性上皮小体機能亢進症, 副甲状腺機能亢進症-原発性, 原発性上皮小体亢進症, 原発性副甲状腺機能亢進症, 原発性上皮小体亢進, 原発性上皮小体機能亢進, 上皮小体機能亢進症-原発性 |
Finnish | Primaarinen lisäkilpirauhasten liikatoiminta |
Russian | GIPERPARATIREOZ PERVICHNYI, ГИПЕРПАРАТИРЕОЗ ПЕРВИЧНЫЙ |
Czech | Primární hyperparatyreóza, hyperparatyreoidismus primární, primární hyperparatyreóza |
Korean | 원발성 부갑상샘 기능항진증 |
Polish | Nadczynność przytarczyc pierwotna |
Hungarian | Primaer hyperparathyreosis, Primaer hyperparathyreoidismus |
Norwegian | Primær hyperparatyreoidisme, Hyperparatyreoidisme, primær, Primær hyperparatyreose, Hyperparatyreose, primær |
Spanish | hiperparatiroidismo primario (trastorno), hiperparatiroidismo primario, Hiperparatiroidismo primario, Hiperparatiroidismo Primario |
Portuguese | Hiperparatiroidismo primário, Hiperparatireoidismo Primário |
French | Hyperparathyroïdie primaire, Hyperparathyroïdie primitive, Hyperparathyroïdisme primaire, Hyperparathyroïdisme primitif |