10 December 2007

HyperParaThyroidism

 

Last Updated: November 7, 2006

Synonyms and related keywords: hyperparathyroidism, calcium levels, phosphorus levels, primary hyperparathyroidism, secondary hyperparathyroidism, tertiary hyperparathyroidism, hypercalcemia, parathyroid carcinoma, asymptomatic primary hyperthyroidism, hypophosphatemia, hyperchloremia, hypercalcemic parathyroid crisis, parathyroid insufficiency, parathyroid hormone, PTH, parathyroid glands, hypercalcemia of malignancy.

AUTHOR INFORMATION

Author: Philip N Salen, MD, Clinical Professor, Department of Emergency Medicine, PA Program, Desales University; Adjunct Clinical Associate Professor, Department of Emergency Medicine, Temple University Medical School, Research Director, Emergency Medicine Education, Saint Luke's Hospital

Philip N Salen, MD, is a member of the following medical societies: American College of Emergency Physicians, Phi Beta Kappa, and Society for Academic Emergency Medicine

Editor(s): Erik D Schraga, MD, Consulting Staff, Permanente Medical Group, Kaiser Permanente, Santa Clara Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital

INTRODUCTION

Background: The parathyroid glands regulate serum calcium and phosphorus levels through the secretion of parathyroid hormone (PTH), which raises serum calcium levels while lowering the serum phosphorus concentration. The regulation of PTH secretion occurs through a negative feedback loop in which calcium-sensing receptors on the membranes of parathyroid cells trigger decreased PTH production as serum calcium concentrations rise.

Primary hyperparathyroidism, which accounts for most presentations of hyperparathyroidism, results from excessive release of PTH and manifests as hypercalcemia. Patients with a finding of hypercalcemia with normal renal function and the absence of malignancy must be suspected of having primary hyperparathyroidism and subsequently tested for an elevated PTH level.

Hyperparathyroidism is often incidentally discovered during routine laboratory testing when hypercalcemia is noted. In 80% of patients with hyperparathyroidism, the symptoms of hypercalcemia are mild or not notable at the time of discovery. Management of these patients is not clear-cut because routine laboratory tests have not been shown to assist in predicting who will develop overt manifestations of the disease. Conversely, overtly symptomatic hyperparathyroid patients (eg, those with urinary tract stones, bone pain, cognitive abnormalities) and those with marked hypercalcemia (calcium level elevated more than 10.2 mg/dL [Jacobs, 1990]) must be referred for parathyroidectomy.

Pathophysiology: Primary hyperparathyroidism is one of the most common causes of hypercalcemia and should be considered in any individual with an elevated calcium level (Boonen, 2004). Primary hyperparathyroidism is usually the result of a single benign adenoma; a minority of patients will have hyperplasia of all 4 parathyroid glands. Parathyroid carcinoma accounts for an insignificant minority (less than 0.5% of patients with hyperparathyroidism).

Asymptomatic primary hyperparathyroidism manifests with serum calcium concentrations only slightly elevated to within 1 mg per deciliter above the upper limit of normal. Within the setting of asymptomatic primary hyperparathyroidism, the parathyroid hormone level is typically 1.5-2 times the upper limit of normal. Hypophosphatemia and hyperchloremia are typically seen only in highly symptomatic patients with advanced hyperparathyroidism.

When hyperparathyroidism manifests with hyperplasia of all 4 glands, familial-genetic syndromes should be considered within the differential diagnosis. Syndromes to be considered include type I and type II multiple endocrine neoplasia (MEN) or less commonly familial hypocalciuric hypercalcemia and hyperparathyroidism-jaw tumor syndrome. Also, a syndrome of familial isolated hyperparathyroidism has been observed. Radiation therapy to the head and neck predisposes subjects to parathyroid tumors.

Secondary hyperparathyroidism occurs when the parathyroid glands become hyperplastic after long-term hyperstimulation and release of PTH. In secondary hyperparathyroidism, elevated PTH levels do not result in hypercalcemia. This has been classically attributed to an underlying state of hypocalcemia in those with chronic renal failure (CRF). However, it has been shown that hypocalcemia itself is not necessary for the development of secondary hyperparathyroidism in this setting. Additional risk factors for the development of secondary hyperparathyroidism include phosphorus retention, intrinsic parathyroid gland abnormalities, diminished serum calcitriol levels, and resistance to PTH by skeletal tissue. Rickets and malabsorption syndromes are rarer causes.

With long-term hyperstimulation, the glands function autonomously and produce high levels of parathyroid hormone even after correction of chronic hypocalcemia. Tertiary hyperparathyroidism refers to hypercalcemia caused by autonomous parathyroid function after long-term hyperstimulation.

Frequency:

  • In the US: Primary hyperparathyroidism has an estimated incidence ranging from 1 in 500 to 1 in 1000 (Boonen, 2004).

Mortality/Morbidity: The majority of patients, who are predominantly elderly, present with mild elevations of serum calcium and are not overtly symptomatic. Usually, the rate of progression of hyperparathyroidism is slow, and it is safe to monitor these patients and manage their disease medically. Although operative mortality is low, there is no evidence that primary hyperparathyroidism with mild hypercalcemia has an adverse effect on survival (Boonen, 2004). Conversely, parathyroidectomy remains the appropriate therapy for symptomatic or complicated primary hyperparathyroidism. There appears to be no differences in complication rate or symptom relief associated with surgery between younger and older patients (Boonen, 2004).

Sex: Most individuals with hyperparathyroidism are older women (Boonen, 2004).

Age: Although hyperparathyroidism can arise at any age, its occurrence rises markedly after age 40 years. Hyperparathyroidism is rare in children.

CLINICAL

History: Most patients with primary hyperparathyroidism are asymptomatic or minimally symptomatic. Because manifestations of hyperparathyroidism are subtle, the disease may run a benign course for years prior to detection. Symptomatic hyperparathyroidism is characterized by vague, nonspecific symptoms including generalized weakness, fatigue, poor concentration, and depression.

Nephrolithiasis resulting in ureteral colic is secondary to serum calcium elevations. Overt bone disease, including subperiosteal bone resorption and osteitis fibrosa cystica, is a serious but rare manifestation of hyperparathyroidism. Proximal muscle weakness may occur, typically affecting the lower limbs more than the upper limbs. Chondrocalcinosis and pseudogout are other potential complications of hyperparathyroidism.

Rarely, hyperparathyroidism may worsen abruptly and cause severe hypercalcemic complications such as profound dehydration, altered mental status, or coma. This is referred to as hypercalcemic parathyroid crisis.

  • A helpful mnemonic, "painful bones, renal stones, abdominal groans, and psychic moans," can be used to recall the typical symptoms of hypercalcemia. Painful bones are the result of abnormal bone remodeling from overproduction of PTH. Renal stones occur from hyperparathyroid-disease–induced hypercalcemia and resultant hypercalciuria. Abdominal groans refers to hypercalcemia-induced ileus. Psychic moans or depression may occur in the presence of persistently elevated serum calcium levels.
  • The most frequent complication of primary hyperparathyroidism is nephrolithiasis, which occurs in about 20% of patients (Boonen, 2004). Renal effects of the disease also include decreased glomerular filtration rate. Hypercalciuria (>300 mg daily calcium excretion) is observed in a significant subset (up to 30%) of patients.
  • Some patients suffer from easy fatigability, a sense of generalized weakness, or mild cognitive impairment.

Physical: No highly specific physical findings are present in hyperparathyroidism.

  • Easily fatigued muscle (particularly proximal muscle groups)
  • Central nervous system
    • Neuropsychiatric illness
    • Altered mental status
    • Coma (severe cases)
  • Cardiovascular system: Signs of hypertension and congestive heart failure may be apparent, although little definitive evidence supports a causal relationship. The association of primary hyperparathyroidism with hypertension has been well documented but remains poorly understood. It is not evident whether parathyroidectomy alters the long-term course of hypertension, as surgery does not reliably result in improvement (Boonen, 2004).
  • Musculoskeletal system
    • Osteoporosis
    • Osteopenia
    • Cystic bone lesions
    • Vertebral collapse
    • Chondrocalcinosis and pseudogout
  • Gastrointestinal
    • Pancreatitis and/or pancreatic calcification
    • Peptic ulcer disease may be present at a higher rate.

Causes:

  • A single parathyroid adenoma is the underlying pathology in 85% of cases.
  • Diffuse hyperplasia of all parathyroid glands occurs in approximately 15% of cases. More than half of these are part of a familial syndrome.
  • Parathyroid carcinoma is a very rare cause of primary hyperparathyroidism.
  • Secondary hyperparathyroidism occurs when the parathyroid glands are chronically stimulated to release parathyroid hormone.
    • Chronic renal failure
    • Malabsorption syndromes
    • Rickets
  • Long-standing secondary hyperparathyroidism may progress into autonomous hypersecretion of parathyroid hormone even after correction of chronic hypocalcemia, termed tertiary hyperparathyroidism.
  • A history of head and neck irradiation appears to predispose individuals to parathyroid tumor formation.

DIFFERENTIALS

Adverse drug reaction to lithium
Adverse reaction to parenteral nutrition
Adverse drug reaction to thiazide diuretics
Cancers producing parathyroid hormone–related protein
Cancers producing ectopic production of 1,25-dihydroxyvitamin D
Familial hypocalciuric hypercalcemia
Berylliosis
Histoplasmosis
Coccidioidomycosis
Immobilization
Leprosy
Lytic bone metastasis
Milk-alkali syndrome
Multiple endocrine neoplasms
Pheochromocytoma
Vasoactive intestinal polypeptide hormone–producing tumor
Ectopic hyperparathyroidism
Exogenous calcium intake
Sarcoidosis

WORKUP

Lab Studies:

  • Elevated parathyroid hormone (PTH) levels in the setting of hypercalcemia establish the diagnosis of hyperparathyroidism. The most common other cause of hypercalcemia in older individuals, hypercalcemia of malignancy, is associated with suppressed levels of PTH.
  • Although measuring the concentration of ionized calcium rather than the total calcium concentration provides added accuracy, one may alternatively use the total serum calcium concentration corrected for the patient's albumin concentration. This can be achieved by adding 0.8 per dL to the total serum calcium value for every 1 g/dL below a serum albumin concentration of 4 g/dL. Those with secondary hyperparathyroidism and associated chronic renal failure are especially prone to hypoalbuminemia so this correction is of particular importance.
  • The normal range for the PTH-intact assay is generally 10-65 pg/mL.
  • A decreased serum phosphate level of less than 2.5 mg/dL (0.81 mmol/L) may be seen.
  • Increased bone turnover may be reflected in elevated levels of markers of bone formation (alkaline phosphatase) and bone resorption (urinary pyridinoline).
  • Urinary calcium excretion may be elevated.
  • A newly introduced immunoradiometric assay for PTH detects only the fully intact molecule and as such may be more accurate than the currently used assay that measures truncated, nonfunctional molecules along with the full-length molecule.
  • Expedited determination of PTH levels in the intraoperative setting with rapid laboratory assays has been used during parathyroid excisions. Because the half-life of PTH is 3-4 minutes, successful excision of all hyperfunctioning parathyroid tissue can be rapidly confirmed in the operating room. The commercially available rapid PTH assay provides an accurate PTH level that can be used intraoperatively to determine quantitatively when all hyperfunctioning parathyroid tissue has been excised. A 50% decrease from the preexcision PTH level in peripheral blood plasma predicts a postoperative correction in serum calcium levels with an overall accuracy of 97% (Irvin, 2000).

Imaging Studies:

  • Radiographs have limited diagnostic value, especially in the early stages of the disease. Normal radiograph findings do not rule out hyperparathyroidism. Radiologic findings are uncommon and are associated with overt, symptomatic disease. Radiographic abnormalities include subperiosteal resorption that is best seen at the radial sides of the phalanges, distal phalangeal tufts, and distal clavicles. However, in the majority of older patients, no specific radiologic manifestations are observed and skeletal radiograph screening is not recommended.
  • Bone-density measurements based on dual energy x-ray absorptiometry (DXA) at the hip and spine should be performed in individuals with primary hyperthyroidism regardless of the age (Boonen, 2004).
  • Imaging of the neck can help locate the parathyroid glands and may demonstrate associated tumors.
  • Cystic bone lesions called brown tumors are seen only in severely affected patients. Soft tissue calcification may be apparent in the joints, kidneys, and lungs with conventional radiographs, and may be more readily evident on bone scans.
  • A CT scan of the spine provides reproducible quantitative estimates of spinal bone density. Serial measurements can provide an early indication of whether or not progressive osteopenia is present.

Other Tests:

  • Several techniques are available for preoperative localization of hypersecreting parathyroid glands.
  • Ultrasonography may be useful but is also operator dependent (Irvin, 2000).
  • The most sensitive and reliable technique is technetium 99m sestamibi tomographic reprojection nuclear scanning because of its ability to produce a 3-dimensional image that can be used for visual reference by the surgeon intraoperatively (Irvin, 2000).

Procedures:

  • If malignancy is suspected, percutaneous needle biopsy may be performed for aspiration cytology and tissue PTH determination.

 

TREATMENT

Prehospital Care: Only in the most severe acute manifestation of hyperparathyroidism, hypercalcemia-induced altered mental status, does management need to begin in the prehospital setting. In such cases, prehospital care should focus on the stabilization of airway, breathing, and circulation. In the field and the emergency department, hydration is the principal primary therapy directed at hypercalcemia.

Emergency Department Care: The ED management of hyperparathyroidism is focused on the treatment of hypercalcemia. Specifically, the goal of treatment is to reduce the calcium level to below 11.5 mg/dL, below the level in which most patients have resolution of hypercalcemia-induced symptoms.

  • Intravenous administration of isotonic saline is the first and most vital step in the management of severe hypercalcemia. Severe hypercalcemia is nearly always accompanied by severe dehydration. When the depleted intravascular volume is restored to reference range, the serum calcium concentration declines by the degree to which dehydration raised it. Subsequent hydration serves to enhance renal excretion of excess calcium.
  • Hypercalcemia is mild in most asymptomatic patients with hyperparathyroidism and may be controlled with gentle hydration with normal saline.
  • For patients with profound hypercalcemia presenting with severe alterations of mental status, loop diuretics facilitate the urinary excretion of calcium and can prevent the volume overload that may accompany the administration of large volumes of saline. Hypercalcemic patients may be destabilized further by fluid and electrolyte disturbances caused by aggressive diuresis and as such should have serial chemistry panels performed for monitoring. Initiation of loop diuretics should only occur after rehydration has taken place.
  • In postmenopausal women with mild hyperparathyroidism, estrogen therapy has been advocated as it may inhibit demineralization of the skeleton and reduce blood calcium levels.
  • Surgery involving open surgical excision with frozen section diagnosis is the only definitive treatment for severe hyperparathyroidism. Successful parathyroidectomy induces normocalcemia in 95-98% of patients with hyperparathyroidism and 82% have symptomatic improvement. Osteoporotic hyperparathyroid patients experience prompt and sustained increase in their bone mineral density after successful parathyroidectomy. Although there is a paucity of studies related to the incidence of fractures in those status post parathyroidectomy, bone mineral density in the femoral neck rises by 6% after 1 year and 14% after 10 years (Irvin, 2000). Although some controversy exists regarding indications for surgery, current National Institutes of Health guidelines for curative, surgical intervention indications are defined by the measurable objective criteria listed below. Approximately 20% of patients with hyperparathyroid disease will meet these criteria (Coker, 2005).
    • Patients with overt clinical manifestations of disease
    • Age younger than 50 years
    • Serum calcium concentration greater than 1 mg/dL above upper limit of normal
    • Urinary calcium excretion greater than 400 mg/d
    • Low or declining bone mineral density
    • Uncertain prospect for successful medical monitoring
    • Patient requesting surgery
    • Poor or uncertain follow-up
    • Coexistent disease that may confound or contribute to disease progression
    • Reduction in creatinine clearance of 30% or more
    • Reduction of bone mineral density greater than 2.5 standard deviations below the bone density of age-, gender-, and race-matched norms (T score below -2.5)
  • Of note, many patients tolerate mild hyperparathyroidism well without operative treatment. Roughly 75% of asymptomatic patients presenting with mild hypercalcemia did well over a 10-year period without significant loss of cortical bone, progressive hypercalcemia, or excessive urinary calcium excretion. Since there are no factors other than the ones listed above that predict which patients with mild disease will experience disease progression, all patients must have serum calcium levels periodically monitored (Irvin, 2000).
  • Because of the improvements in radiopharmaceutical screening and the availability of the intraoperative, rapid PTH assay, minimally invasive parathyroidectomies under local anesthesia are now being performed with patients being discharged several hours postoperatively. This technique has altered the management and the surgical indications for hyperparathyroid for some. For example, symptomatic elderly patients with comorbid disease who were previously denied surgery because of risks related to anesthesia and bilateral neck dissection are now potential candidates for minimally invasive parathyroidectomy. Furthermore, in centers in which limited parathyroidectomy is available, asymptomatic patients with moderate hypercalcemia (0.4-0.9 mg/dL above normal) can be considered for earlier parathyroidectomy before severe bone loss or kidney damage occurs (Irvin, 2000).

Consultations: Surgical consultation is necessary for patients with severe hypercalcemia resulting from hyperparathyroidism that meet current NIH guidelines for curative, surgical intervention. New techniques for identifying and operating on hyperactive parathyroid glands have improved the success rate of parathyroidectomy as measured by a return to normocalcemia in 98% of patients and also have simplified the operation from a bilateral neck operation under general anesthesia to a simpler outpatient procedure. The new parathyroidectomy technique involves performing the procedure through a small incision under local anesthesia with limited, target-specific dissection. Excision of the hyperfunctioning gland is confirmed in the operating room by a quantitative decrease in the plasma PTH level, ensuring that all hypersecreting tissue has been removed. The failure rate of this minimally invasive procedure is only approximately 1.5% (Irvin, 2000).

  • When normal glands are found in association with one enlarged adenomatous gland, excision of the single adenoma usually leads to a cure or eliminates symptoms.
  • The surgical approach usually entails removal of a single enlarged gland; however, all glands must be examined in some way to eliminate the possibility that more than one gland is abnormal. Multiglandular disease, identified by quantitative biochemical frozen section, is present in 5% of patients with primary hyperparathyroidism and must be recognized and treated at the time of operation to ensure operative success (Irvin, 2000).
  • With multiple gland hyperplasia, total parathyroidectomy is performed with immediate transplantation of a portion of a removed minced parathyroid gland into the muscles of the forearm so that, even if parathyroid gland hyperfunction recurs, surgical excision is easier from the ectopic site in the arm.
  • A decline in serum calcium level occurs within 24 hours of successful surgery. Additionally, serum PTH levels fall within minutes of a successful parathyroidectomy. Intraoperative measurement of PTH can be useful in locating obscure glands through differential venous sampling, measuring increased hormone secretion after massage of specific areas, and correctly identifying the excision of abnormal parathyroid tissue when it is not easily recognized (Irvin, 2000).
  • Usually, blood calcium level falls to low reference range values for 3-5 days until the remaining parathyroid tissue resumes hormone secretion. Severe postoperative hypocalcemia is likely only if osteitis fibrosa cystica is present or if injury to all the normal parathyroid glands occurs during surgery.

 

MEDICATION

Intravenous hydration with isotonic sodium chloride solution adequately reduces calcium levels in most patients with hyperparathyroid-induced hypercalcemia.

For postmenopausal female patients who do not undergo surgery, estrogen may be beneficial to help maintain bone mass. However, a 1991 National Institutes of Health (NIH) Consensus Conference on Management of Asymptomatic Hyperparathyroidism did not recommend estrogen therapy, citing insufficient cumulative experience to warrant a recommendation.

The use of other calcium-lowering agents, such as bisphosphonates, plicamycin, and calcitonin, are used to treat oncologic causes of hypercalcemia and are not used for hyperparathyroidism.

Cinacalcet, a calcimimetic drug that reduces PTH secretion by altering the function of parathyroid calcium-sensing receptors, can be initiated in patients with hypercalcemia secondary to parathyroid carcinoma, secondary hyperparathyroidism, and primary hyperparathyroidism. For hypercalcemia from primary hyperparathyroidism or parathyroid malignancy, the starting dose is usually 30 mg orally twice daily. For those with secondary hyperparathyroidism, the starting dose is 30 mg once daily. After initiation of cinacalcet, measure the serum calcium level within 1 week to allow dose adjustment.

Drug Category: Loop diuretics -- These agents may be helpful following hydration in individuals who are hypercalcemic.

Drug Name
Furosemide (Lasix) -- Increases excretion of water and calcium. Interferes with chloride-binding cotransport system by inhibiting the reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule.

Adult Dose
40 mg PO bid for patients already taking furosemide; give PO dose as IV bolus

Pediatric Dose
1 mg/kg PO/IV as single dose

Contraindications
Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion

Interactions
Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently

Pregnancy
C - Safety for use during pregnancy has not been established.

Precautions
Observe for blood dyscrasias and liver or kidney damage; perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Drug Category: Hormonal therapy -- Hormone therapy is indicated in postmenopausal females with hyperparathyroidism.

Drug Name
Estrogen (Premarin) -- Reduces bone resorption resulting from hyperparathyroidism.

Adult Dose
1.25 mg PO qd

Pediatric Dose
Administer as in adults

Contraindications
Documented hypersensitivity; known or suspected pregnancy; breast cancer, undiagnosed abnormal genital bleeding, active thrombophlebitis, or thromboembolic disorders; history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast or prostatic malignancy)

Interactions
May reduce hypoprothrombinemic effect of anticoagulants; coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes may reduce estrogen levels; pharmacologic and toxicologic effects of corticosteroids may occur as a result of estrogen-induced inactivation of hepatic cytochrome P-450 enzyme; loss of seizure control has been noted when administered concurrently with hydantoins

Pregnancy
X - Contraindicated in pregnancy

Precautions
Certain patients may have undesirable manifestations of excessive estrogenic stimulation (eg, abnormal or excessive uterine bleeding, mastodynia); may cause some degree of fluid retention (exercise caution); prolonged unopposed therapy may increase risk of endometrial hyperplasia

Drug Category: Calcimimetic agents -- Calcium regulator, calcimimetic agent also used in hypercalcemia of malignancy. These agents bind to and modulate the parathyroid calcium-sensing receptor, increase sensitivity to extracellular calcium, and reduce PTH secretion.

Drug Name
Cinacalcet (Sensipar) -- Directly lowers PTH levels by increasing sensitivity of calcium-sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium level decrease. Indicated for hypercalcemia with parathyroid carcinoma.

Adult Dose
30 mg PO qd initially; titrate q2-4wk as needed to normalize calcium levels by sequential doses of 30 mg bid, 60 mg bid, 90 mg bid, and 90 mg tid/qid
Take with meals or immediately following; do not crush, chew, or cut tablets

Pediatric Dose
Not established

Contraindications
Documented hypersensitivity

Interactions
Strong CYP450 2D6 inhibitor; may increase serum levels of CYP 2D6 substrates (eg, flecainide, vinblastine, thioridazine, tricyclic antidepressants); coadministration with CYP450 3A4 inhibitors (eg, ketoconazole, erythromycin, itraconazole) may decrease cinacalcet clearance

Pregnancy
C - Safety for use during pregnancy has not been established.

Precautions
Serum calcium reduction may cause lowered seizure threshold, paresthesia, myalgia, cramping, and tetany; monitor calcium and phosphorus levels closely within 1 wk following initial dose or dose changes, and then monthly (secondary hyperparathyroidism) and q2mo (parathyroid carcinoma); do not initiate treatment if serum calcium level is below 8.4 mg/dL; adynamic bone disease may occur if iPTH levels suppressed below 100 pg/mL; caution with hepatic impairment; common adverse effects include nausea and vomiting

 

FOLLOW-UP

Further Inpatient Care:

  • Admit patients with significant symptoms from hyperparathyroid-induced hypercalcemia and substantial elevations of calcium levels.
  • Markedly symptomatic patients or those with significant electrolyte disturbances should be evaluated by endocrinologists and surgeons experienced in parathyroid removal.

Further Outpatient Care:

  • Calcium levels must be periodically monitored for several months postparathyroidectomy.
  • If calcium levels begin to rise postoperatively, the patient needs to be evaluated for possible accessory parathyroid glands.
  • Monitor asymptomatic patients for worsening hypercalcemia, deteriorating bone density or renal function, and other complications of hyperparathyroidism.
  • If the serum calcium concentration falls below 8 mg/dL post parathyroidectomy with a concomitant rise in serum phosphate level, consider the possibility of postsurgical hypoparathyroidism.

Deterrence/Prevention:

  • Although it is prudent for patients to refrain from the ingestion of more calcium than is recommended for adults (1200-1500 mg/d), it is also important not to restrict calcium intake excessively (to less than 750 mg/d), as calcium-poor diets may promote processes associated with excessive secretion of PTH.
  • Because many patients with asymptomatic primary hyperparathyroidism have levels of 25-hydroxyvitamin D that are at the lower end of the normal range or frankly low, the addition of a low level of supplementation achievable with a multivitamin (400 IU of vitamin D daily) is advisable.

Complications:

  • Maternal hyperparathyroidism can lead to profound hypocalcemia and tetany, coma, and death in newborns in a syndrome known as neonatal severe hyperparathyroidism.
  • Nocturia and polyuria may result from the effects of elevated calcium levels on the renal tubule.
  • Approximately 20% of patients with hyperparathyroidism have nephrolithiasis.
  • CNS disturbances, coma, and death may result from markedly elevated serum calcium levels when left untreated.
  • Skeletal sequelae (eg, pathologic fracture)
  • Heart failure
  • Surgical complications
    • Hypoparathyroidism
    • Recurrent laryngeal nerve damage
    • Hemorrhage
    • Infection
    • Unsuccessful surgery (5%)

Prognosis:

  • The prognosis is excellent for patients after successful parathyroidectomy.
  • Asymptomatic patients who do not have indications for surgery have an excellent prognosis. Significant bone loss and other symptoms may be absent for years in subsequent follow-up visits.
  • Secondary hyperparathyroidism is associated with a poor prognosis, likely owing to underlying advanced chronic renal failure and resultant chronic hypocalcemia.

Patient Education:

  • Educate patients about prescribed medications.
  • Educate patients regarding the importance of periodic laboratory and radiologic testing.

 

BIBLIOGRAPHY

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  • External Link:

    http://www.emedicine.com/emerg/topic265.htm

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