Hyperparathyroidism

Aka: Hyperparathyroidism, Primary Hyperparathyroidism

II. Pathophysiology

  1. Overactive Parathyroid Glands (>=1 of 4 glands)
  2. Produce excessive Parathyroid Hormone (PTH)
  3. Results in disorder of bone metabolism

III. Epidemiology

  1. Prevalence
    1. Women: 2-3 cases per 1000 women over age 65 years
    2. Men: 1 case per 1000 men over age 65 years
  2. Ages
    1. Range: 40-70 years old
    2. Mean: 55 years old

IV. Causes: Primary Hyperparathyroidism

  1. Single Parathyroid Adenoma (82 to 85%)
  2. Parathyroid Gland Hyperplasia or hypertrophy (15%)
  3. Parathyroid Malignancy (rare, accounts for 0.5 to 3% of Primary Hyperparathyroidism)
  4. Familial Hyperparathyroidism (10-20%): Younger patients
    1. Multiple Endocrine Neoplasia Type I (MEN I)
    2. Multiple Endocrine Neoplasia Type I (MEN II)
    3. Familial Hypocalciuric Hypercalcemia
    4. Hyperparathyroidism-Jaw Tumor Syndrome
    5. Neonatal severe Primary Hyperparathyroidism
  5. Other Parathyroid related causes
    1. Lithium Therapy
    2. External neck radiation exposure
    3. Neck surgery with Parathyroid injury or resection
  6. Tertiary Hyperparathyroidism
    1. Accelerated response to chronic Hypocalcemia (in advanced Renal Failure)
    2. Parathyroid over-produces PTH causing Hypercalcemia

V. Causes: Secondary Hyperparathyroidism

  1. Vitamin D Deficiency
  2. Decreased calcium intake
  3. Renal Osteodystrophy
    1. Chronic Kidney Disease stage 4 or stage 5 and
    2. Decreased 1,25 dihydroxyvitamin D
    3. Hyperphosphatemia
    4. Hypocalcemia
  4. Normocalcemic Hyperparathyroidism (associated with Osteoporosis)
    1. Diagnosis of exclusion after ruling-out Vitamin D Deficiency and Chronic Kidney Disease

VI. Symptoms

  1. See Hypercalcemia
  2. Asymptomatic Hypercalcemia (up to 80% of cases)

VII. Diagnosis

  1. Mnemonic (classic presentation is uncommon)
    1. Stones
    2. Bones
    3. Abdominal groans
    4. Psychic moans
  2. Constellation of findings
    1. See Hypercalcemia
    2. Calcium oxalate renal stones (Nephrolithiasis)
    3. Bony changes
      1. Osteitis fibrosa
      2. Salt and pepper skull
      3. Bone resorption
    4. Acute Pancreatitis
    5. Psychosis and depression

VIII. Labs

  1. Parathyroid Hormone (PTH) Level elevated
    1. Measure Intact PTH
    2. See Parathyroid Hormone for algorithm
  2. Serum Electrolyte abnormalities
    1. Hypercalcemia (Use Corrected Serum Calcium)
      1. Draw Fasting with minimal Occlusion
      2. Discontinue Thiazide Diuretics for 2 weeks before
      3. Repeat serum testing in 2 weeks if normal
    2. Hyperchloremia
    3. Hypophosphatemia
    4. Hypokalemia
  3. Miscellaneous
    1. 1,25 Dihydroxyvitamin D3
      1. Indicated if Serum Calcium low
  4. Urine Calcium and Phosphate
    1. Hypercalciuria (24 hour Urine Calcium)
    2. Hyperphosphaturia
  5. Arterial Blood Gas
    1. Non-Anion Gap Metabolic Acidosis
  6. Renal Function tests
    1. Creatinine Clearance

IX. Imaging

  1. Classic XRay Findings
    1. Skull XRay
      1. "Salt and pepper" skull
    2. Chest XRay
      1. Distal Clavicle resorption
    3. Hand XRay
      1. Second and third middle phalange bone resorption
    4. Dental XRay
      1. Bone resorption of Lamina dura around teeth
  2. Sestamibi Technetium Tc 99mParathyroid Scan
    1. Test Sensitivity for localizing adenoma: 95%
    2. Causes of non-localizing scan
      1. Ectopic PTH production
      2. Diagnostic error
      3. Four-gland hyperplasia
  3. End-organ evaluation
    1. Renal Ultrasound
    2. Bone Densitometry (DEXA Scan)
      1. Lumbar Spine
      2. Hip
      3. Forearm

X. Differential Diagnosis

  1. See Hypercalcemia
  2. Familial Benign Hypocalciuric Hypercalcemia
    1. Does not improve with surgery, unlike primary disease
    2. Calcium to Creatinine ratio <0.01

XI. Management: Medical Monitoring

  1. Indications
    1. Asymptomatic patients without surgical indications
    2. Serum Calcium level only mildly increased
    3. No priot life-threatening Hypercalcemia
    4. Normal Renal Function
      1. Creatinine Clearance >70%
      2. No Nephrolithiasis
      3. No Nephrocalcinosis
    5. Normal Bone Mineral Density (Osteopenia or better)
  2. Avoid provocative factors
    1. Thiazide Diuretics and Lithium
    2. Avoid Volume depletion (maintain hydration)
    3. Avoid prolonged bedrest or inactivity
    4. Avoid High Calcium diet
    5. Avoid Vitamin D supplementation
  3. Encourage moderate Physical Activity
    1. Minimize bone resorption
  4. Encourage 64 ounces non-caffeinated fluid per day
    1. Minimize risk of Nephrolithiasis
  5. Encourage moderate calcium intake (1000 mg/day)
    1. Low Calcium diet may surge Parathyroid Hormone
  6. Medications
    1. Calcium Lowering Therapy
      1. See Hypercalcemia
    2. Pharmacologic Measures: Reduce bone resorption
      1. Estrogen Replacement Therapy (Postmenopausal)
      2. Bisphosphonates

XII. Management: Surgery

  1. Precautions
    1. Re-evaluate on a periodic basis
    2. Up to 15% of originally asymptomatic Hyperparathyroidism cases develop a surgical indication within 4.7 years
      1. Yu (2011) QJM 104(6): 513-21 [PubMed]
  2. Indications in Primary Hyperparathyroidism
    1. Serum Calcium >12 mg/dl (or >1 mg/dl above the upper limit of normal)
    2. Hypercalcemic Crisis (Serum Calcium >14 mg/dl)
    3. 24 hour Urine Calcium >400 mg/day
    4. Osteoporosis (or T-Score <-2.5 at hip, spine or wrist)
    5. Osteitis fibrosa cystica
    6. Nephrolithiasis
    7. Nephrocalcinosis
    8. Young patient age (e.g. age <50 years)
    9. Exacerbating factors
      1. Dehydration
      2. Immobile patient
    10. Creatinine Clearance <60 ml/min/1.73m2 or 30% below age-matched peers
    11. Persistent Hypercalcemia symptoms (esp neuromuscular)
  3. Efficacy
    1. Successful in up to 95% of cases
    2. Few complications
  4. Single Parathyroid Adenoma
    1. Surgery to locate and remove adenoma
    2. Biopsy a second gland to rule out atrophy
  5. Parathyroid hyperplasia or hypertrophy
    1. Remove 3.5 glands
    2. Autotransplant tissue into arm muscle

XIII. Monitoring of medically managed patients

  1. Every 6 month labs
    1. Serum Calcium
  2. Every 12 month labs
    1. Serum Creatinine
    2. Urinary Calcium Excretion
  3. Every 6-12 month labs for women
    1. Bone Density (DEXA Scan)

XIV. References

  1. Spiegel in Goldman (2000) Cecil Medicine, p. 1402-5
  2. (1991) Ann Intern Med 114:593-7 [PubMed]
  3. Bilezikian (2002) J Clin Endocrinol Metab 87:5353-61 [PubMed]
  4. Taniegra (2004) Am Fam Physician 69(2):333-40 [PubMed]
  5. Michels (2013) Am Fam Physician 88(4): 249-57 [PubMed]

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Related Studies

Ontology: Hyperparathyroidism (C0020502)

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, ﾌｸｺｳｼﾞｮｳｾﾝｷﾉｳｺｳｼﾝｼｮｳ, ﾌｸｺｳｼﾞ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
Derived from the NIH UMLS (Unified Medical Language System)

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 ｹﾞﾝﾊﾟﾂｾｲﾌｸｺｳｼﾞ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
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Parathyroid Disease

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