Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Published Ahead of Print
    • Archive
    • Supplemental Issues
    • Collections - French
    • Collections - English
  • Info for
    • Authors & Reviewers
    • Submit a Manuscript
    • Advertisers
    • Careers & Locums
    • Subscribers
    • Permissions
  • About CFP
    • About CFP
    • About the CFPC
    • Editorial Advisory Board
    • Terms of Use
    • Contact Us
  • Feedback
    • Feedback
    • Rapid Responses
    • Most Read
    • Most Cited
    • Email Alerts
  • Blogs
    • Latest Blogs
    • Blog Guidelines
    • Directives pour les blogues
  • Mainpro+ Credits
    • About Mainpro+
    • Member Login
    • Instructions
  • Other Publications
    • http://www.cfpc.ca/Canadianfamilyphysician/
    • https://www.cfpc.ca/Login/
    • Careers and Locums

User menu

  • My alerts

Search

  • Advanced search
The College of Family Physicians of Canada
  • Other Publications
    • http://www.cfpc.ca/Canadianfamilyphysician/
    • https://www.cfpc.ca/Login/
    • Careers and Locums
  • My alerts
The College of Family Physicians of Canada

Advanced Search

  • Home
  • Articles
    • Current
    • Published Ahead of Print
    • Archive
    • Supplemental Issues
    • Collections - French
    • Collections - English
  • Info for
    • Authors & Reviewers
    • Submit a Manuscript
    • Advertisers
    • Careers & Locums
    • Subscribers
    • Permissions
  • About CFP
    • About CFP
    • About the CFPC
    • Editorial Advisory Board
    • Terms of Use
    • Contact Us
  • Feedback
    • Feedback
    • Rapid Responses
    • Most Read
    • Most Cited
    • Email Alerts
  • Blogs
    • Latest Blogs
    • Blog Guidelines
    • Directives pour les blogues
  • Mainpro+ Credits
    • About Mainpro+
    • Member Login
    • Instructions
  • RSS feeds
  • Follow cfp Template on Twitter
  • LinkedIn
  • Instagram
Review ArticlePractice

Primary hyperparathyroidism

Update on presentation, diagnosis, and management in primary care

Shelley Pallan and Aliya Khan
Canadian Family Physician February 2011; 57 (2) 184-189;
Shelley Pallan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: pallans@mcmaster.ca
Aliya Khan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • eLetters
  • Info & Metrics
  • PDF
Loading

Abstract

Objective To discuss the presentation, diagnosis, and management of primary hyperparathyroidism (PHPT) in family medicine.

Quality of evidence MEDLINE was searched from 2002 to 2009 using the terms presentation, diagnosis, and treatment of PHPT. Proceedings and guidelines from the Third International Workshop on Primary Hyperparathyroidism in May 2008 were reviewed in detail. Most studies offered level II and III evidence, although there were a number of single randomized controlled trials on PHPT (level I evidence). References from pertinent papers were also searched for relevant articles. Articles most relevant to family medicine and primary care practitioners are presented.

Main message Primary hyperparathyroidism is the most common cause of hypercalcemia in outpatients. In the Western world, most patients with PHPT present with nonspecific symptoms such as fatigue, mood disturbances, and cognitive impairments. Diagnosis is established when intact parathyroid hormone levels are elevated or at the high end of the normal range in the setting of elevated total or ionized calcium levels (following exclusion of conditions that can mimic PHPT). Criteria for surgery have recently been modified. Surgery is always a suitable option in those with symptomatic PHPT and no contraindications. Those with contraindications or with asymptomatic PHPT not meeting the criteria for surgery can generally be safely monitored and considered for medical management. This might include treatment with bisphosphonates, hormone replacement therapy, raloxifene, or calcimimetic agents; however, there are currently no fracture data for any of these options.

Conclusion The definitive therapy for symptomatic and asymptomatic PHPT is parathyroidectomy. In patients with asymptomatic PHPT not meeting the criteria for surgery, monitoring is safe and medical management designed to target skeletal protection or lower serum calcium is a suitable option.

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in the outpatient clinical setting.1 This condition can occur at any age, but it more commonly affects those older than 50 years of age and postmenopausal women.1,2 The prevalence of PHPT ranges from 1 to 4 per 1000 people.3

The 4 parathyroid glands are located in the neck on the posterior surface of the thyroid gland, which is situated between the cricoid cartilage and the suprasternal notch on the anterior surface of the trachea. Uncommonly, the parathyroid glands might also be found in the carotid sheath, anterior mediastinum, and intrathyroidal tissue. The chief cells of the parathyroid glands secrete parathyroid hormone (PTH), which is the main regulator of calcium homeostasis in the body. In response to low serum ionized calcium levels, PTH production and secretion are upregulated. Parathyroid hormone normalizes calcium by enhancing calcium reabsorption in distal renal tubular cells, stimulating osteoclast-mediated bone resorption and catalyzing the conversion of 25-hydroxyvitamin D3 (25[OH]D) to 1,25-dihydroxyvitamin D3, which in turn enhances calcium reabsorption from the gastrointestinal tract.3

Patients with PHPT have abnormal regulation of PTH secretion. Primary hyperparathyroidism is characterized by elevated serum calcium in the setting of elevated or upper normal PTH levels; PTH levels that fall within the upper normal range are inappropriately elevated in the presence of high calcium levels. Almost 90% of PHPT cases are caused by sporadic PTH-secreting solitary adenomas. Multiglandular hyperplasia and parathyroid carcinoma account for only about 5% and less than 1% of PHPT cases, respectively.4 Ectopic locations of adenomatous parathyroid tissue, such as intrathoracic adenomas,5 have also been reported.

Primary hyperparathyroidism is also associated with rare familial disorders, including multiple endocrine neoplasia (MEN) type 1 and type 2A syndromes, familial hypocalciuric hypercalcemia (FHH), familial hyperparathyroidism–jaw tumour syndrome, neonatal severe hyperparathyroidism, and familial isolated hyperparathyroidism.3 The MEN type 1 and type 2A syndromes are caused by mutations in the MEN1 and RET genes, respectively; they are hereditary syndromes associated with multiple endocrine tumours, including parathyroid tumours.6 Familial hypocalciuric hypercalcemia mimics PHPT and is caused by an inactivating mutation of the calcium-sensing receptor gene, which makes the receptor less sensitive to calcium in the parathyroid glands and the kidneys. As a result, a higher serum calcium level is required to reduce PTH secretion. As the mutation also affects the calcium-sensing receptors in the kidney, renal calcium clearance is inappropriately low. Familial hypocalciuric hypercalcemia is inherited as an autosomal dominant condition with high penetrance and is a benign cause of hypercalcemia.6,7 Familial hyperparathyroidism–jaw tumour syndrome, associated with mutations in the HRPT2 gene,8 is a rare autosomal dominant condition affecting young adults, which can present as single parathyroid adenomas, bony lesions of the jaw, renal hamartomas, or cystic kidney disease.9

Certain drugs, such as thiazide drugs and lithium, might also alter calcium homeostasis. Thiazide diuretics might unmask underlying PHPT, as they cause mild hypercalcemia by reducing urinary calcium excretion; PHPT is likely if hypercalcemia persists after stopping the medication.10 Although most patients taking lithium therapy do not develop hypercalcemia, lithium decreases the parathyroid gland’s sensitivity to calcium, and shifts the set-point of the calcium-PTH curve to the right, causing increases in serum levels of calcium and PTH.11 Hence, lithium can also unmask pre-existing parathyroid adenomas or induce parathyroid hyperplasia with prolonged use. A history of radiation exposure to the head and neck region and radioactive iodine therapy might also contribute to the development of PHPT, but there are only small case series supporting this pathogenesis (level II evidence).12,13

Quality of evidence

We searched MEDLINE from 2002 to 2009 using the terms presentation, diagnosis, and treatment of PHPT. Proceedings and guidelines from the Third International Workshop on Primary Hyperparathyroidism in May 2008 were thoroughly reviewed. Level of evidence is cited where appropriate. Most studies offered level II and III evidence, although there were a number of single randomized controlled trials on PHPT (level I evidence). Reference lists of pertinent papers were also searched for relevant articles. Articles most relevant to family medicine and primary care practitioners are presented.

Main message

Clinical presentation

Patients with PHPT might present with symptomatic hypercalcemia, asymptomatic hypercalcemia detected incidentally, or normocalcemic hyperparathyroidism.

Symptomatic hypercalcemia occurs with longstanding elevated levels of PTH. It is usually found in developing countries where biochemical screening is not widely available. The patients in such countries are younger and might have debilitating renal and skeletal complications of hyperparathyroidism at the initial presentation of PHPT.14 The spectrum of bone disease in PHPT can include bony pain, low bone mineral density (BMD) commonly most substantial at cortical sites, fragility fractures, or rarely PHPT bone disease (ie, osteitis fibrosa cystica). Renal manifestations of PHPT include nephrolithiasis, nephrocalcinosis, polyuria, and renal insufficiency. Patients with PHPT might also have gastrointestinal symptoms of nausea, vomiting, peptic ulcer disease, constipation, and pancreatitis. Neuropsychiatric disturbances vary and include lethargy, decreased cognitive and social function, depressed mood, psychosis, and coma in those with severe hypercalcemia.15 Recent randomized controlled trials have provided inconsistent results about the exact nature of neuropsychological dysfunction in asymptomatic PHPT (level I evidence).16–18 Rheumatologic diseases such as gout and pseudogout might also be associated with PHPT.19 Although patients with PHPT sometimes have left ventricular hypertrophy, conduction abnormalities, endothelial dysfunction, and shortened QT intervals, the effects of mild PHPT on the development of cardiovascular disease are not known.20 In recent years, initial presentation of PHPT as brown tumours of the maxilla,21 sphenoid sinus, and occipital bone22; nephrocalcinosis; and depressive psychosis23 have also been reported outside of North America. It is important to note that the symptoms of hypercalcemia do not necessarily correlate with the degree of biochemical abnormality. A hypercalcemic crisis is usually precipitated by an intercurrent illness or volume depletion, and generally presents with very high serum calcium and PTH levels, as well as a combination of the findings listed above.

The classic features of hypercalcemia are very uncommon initial complaints in the Western world. Most patients in developed countries have asymptomatic forms of PHPT or nonspecific symptoms such as fatigue, mild depression, or cognitive impairment. This article will focus mainly on the diagnosis and medical management of asymptomatic PHPT.

Less commonly, patients can present with normal serum calcium and persistently elevated PTH levels in the absence of vitamin D insufficiency or chronic kidney disease. This form of presentation is termed normocalcemic hyperparathyroidism. These patients might initially present for evaluation of low BMD, osteoporosis, or fragility fractures.24 The natural history of normocalcemic hyperparathyroidism is not well known, but some patients progress to hypercalcemic hyperparathyroidism, as reported in a few observational studies (level II evidence).25 Before confirming this diagnosis, it is essential to exclude vitamin D deficiency and chronic kidney disease, as these conditions can present with increased PTH levels and normal calcium.

There are no specific physical findings in PHPT, and parathyroid adenomas or carcinomas are rarely palpable; however, it is important to exclude neck masses. Band keratopathy, which is the deposition of calcium phosphate in the exposed regions of the cornea (detected by a slit-lamp examination) is exceedingly rare and occurs with very high serum calcium and phosphate levels.15

Laboratory findings

Primary hyperparathyroidism is diagnosed when intact PTH levels are elevated or at the high end of the normal range in the setting of elevated total or ionized calcium levels. Because about 40% of calcium is bound to albumin, serum calcium levels should be corrected for albumin. Repeat measurements (usually 3) of calcium and PTH should be taken before establishing the diagnosis of PHPT. The main goal of further laboratory testing is to rule out other causes of hypercalcemia. Findings suggestive of FHH include a urinary calcium–to–creatinine clearance ratio of less than 0.01. It is important to distinguish FHH from PHPT because a parathyroidectomy is not recommended for FHH, as it does not cure the condition. Family members of the patient should also be assessed for FHH if it is suspected. The levels of 25(OH)D can be measured in order to exclude vitamin D insufficiency as a cause of elevated PTH. Repletion with vitamin D increases urinary calcium excretion in mild PHPT but not in FHH.6 Moreover, vitamin D insufficiency is commonly seen in PHPT and has been linked to lower BMD, higher bone turnover (level II evidence),26 higher risk of postoperative hypocalcemia, and hungry-bone syndrome after parathyroidectomy.27

Renal function tests can indicate the extent of kidney involvement in the hyperparathyroid state. In patients who present with family history of multiple endocrine tumours, genetic testing for mutations in the MENIN and RET genes should be considered. Evaluating serum and 24-hour urinary calcium excretion in the family members of the patient is helpful in confirming the presence of a familial parathyroid condition. Analysis for mutations in the calcium-sensing receptor gene can be completed if a de novo case of FHH is suspected. Other tests helpful in establishing the diagnosis of PHPT include serum phosphorus levels (decreased or low-normal in PHPT). The markers of bone turnover, such as osteocalcin and bone-specific alkaline phosphate, might be mildly elevated in cases of PHPT and reflect increased bone remodeling.2,6,28

Excluding other causes of hypercalcemia is necessary before confirming the diagnosis. An accurate history of skeletal fragility, renal disease, calcium intake, symptoms suggestive of malignancy, thyroid disease, adrenal insufficiency, previous bariatric surgery, and pancreatic disease, and a thorough review of medications including thiazide diuretics and lithium are necessary. After exclusion of malignancy, granulomatous diseases, or other causes of hypercalcemia, PHPT can be confirmed. This is particularly important if the serum PTH is not elevated.

Management

Definitive therapy for symptomatic and asymptomatic PHPT is parathyroidectomy. A hypercalcemic crisis is managed by volume repletion, administration of loop diuretics once the patient is euvolemic, and pamidronate or zoledronate to further decrease bone resorption. This article focuses on the current guidelines for the surgical and medical management of asymptomatic PHPT, as this is the most common presentation in Canada.

Surgical management: The decision for parathyroid surgery in asymptomatic PHPT is dependent upon patient characteristics such as age, creatinine clearance, and BMD. The guidelines for parathyroid surgery in asymptomatic PHPT according to the Third International Workshop on Primary Hyperparathyroidism are listed in Table 1.29 In the absence of nephrolithiasis, a 24-hour urine calcium level greater than 10 mmol/d is no longer an indication for parathyroidectomy, as urinary calcium excretion is also affected by other factors, including age, ethnicity, sex, dietary calcium intake, vitamin D stores, and glomerular filtration rate (level III evidence).25,29 However, a 24-hour urine calcium measurement should still be ordered in the initial evaluation of patients suspected to have PHPT in order to rule out the diagnosis of FHH. The new international guidelines state that a creatinine clearance below 60 mL/min is an indication for surgery (compared with a creatinine clearance reduced by 30% recommended by older guidelines published in 2002). A creatinine clearance less than 60 mL/min might be associated with further rises in PTH in PHPT, and it also represents stage 3 renal insufficiency as defined by the Kidney Disease Outcomes Quality Initiative guidelines. Declining renal function might thus further fuel the hyperparathyroid condition, and surgery is recommended (level III evidence).29

View this table:
  • View inline
  • View popup
Table 1.

Guidelines for parathyroid surgery in patients with asymptomatic PHPT

Primary hyperparathyroidism is associated with decreases in BMD, particularly at cortical skeletal sites; however, the relationship between BMD and fracture risk in asymptomatic PHPT has not been established. Expert consensus guidelines recommend parathyroid surgery when the T score is −2.5 or less at the lumbar spine, femoral neck, total hip, or distal one-third of the radius in perimenopausal and postmenopausal women, and in men aged 50 and older. For premenopausal women and in men younger than 50 years of age, a Z score of less than −2.5 is recommended for consideration of pararthyroid surgery (level III evidence).29 In an observational study of patients with asymptomatic PHPT followed by conservative management for 15 years, serum calcium was found to be stable without surgery; however, calcium was noted to rise after 13 years of follow-up, suggesting the need for long-term monitoring (level II evidence).30

In patients with mild PHPT, studies have shown that parathyroidectomy, as compared with medical observation, increased BMD at the femoral neck and total hip (level I evidence)16 and lumbar spine (level I evidence).18 These studies also showed normalization of serum calcium and PTH with surgery. Fracture risk appears to decrease with parathyroidectomy in those with asymptomatic PHPT. In those who do not proceed to parathyroidectomy, regular monitoring of serum calcium and 3-site BMD measurements are recommended.

Imaging of the parathyroid before surgery is of value, particularly if a limited exploration is planned. Imaging options include technetium 99m–labeled sestamibi scanning, ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography. A sestamibi scan is a widely used noninvasive imaging localizing technique; it has an accuracy rate of 50% to 70%, but can be nonlocalizing in patients with multiglandular parathyroid disease or small adenomas.31 Imaging should not be used to establish the diagnosis of PHPT or to screen patients for surgical referral. It is essential to ensure that the surgery is performed by an experienced surgeon. The type of surgical technique employed, be it total open parathyroidectomy or a minimally invasive procedure with or without the use of intraoperative PTH assays, will be chosen by the surgeon based on his or her surgical expertise.31

Medical management: In patients with asymptomatic PHPT, medical management designed to target skeletal protection or lower serum calcium might be a suitable option. It can be of value for those with contraindications to, or those who do not wish to have, surgery. Among drugs in the bisphosphonate class, alendronate in particular has been shown to decrease bone turnover and increase BMD in PHPT (level I evidence).32–34 Hormone replacement therapy (HRT) also improved BMD in postmenopausal women with mild PHPT (level I evidence).35 It is not known whether these treatments also reduce fracture risk.36

Bisphosphonates are usually the agent of choice for skeletal protection, owing to the adverse effects of HRT related to cardiovascular disease and breast cancer. Raloxifene, a selective estrogen receptor modulator, decreases bone turnover in postmenopausal women with PHPT, but more research is needed to elucidate its effects on BMD (level I evidence).37 Bisphosphonates, HRT, and raloxifene do not lower serum calcium or PTH levels. A calcimimetic agent, cinacalcet, reduces both serum calcium and PTH levels in patients with mild PHPT but does not have any effects on bone turnover or BMD.36 Cinacalcet is not routinely used for management of asymptomatic PHPT, and its use is generally limited to treating symptomatic hypercalcemia. The most recent guidelines for the follow-up of patients who are being medically managed for PHPT are listed in Table 2.29

View this table:
  • View inline
  • View popup
Table 2.

Guidelines for medical surveillance for patients with asymptomatic PHPT

Patients should be encouraged to engage in physical activity (to decrease bone resorption) and to maintain adequate hydration (to reduce the risk of developing serious hypercalcemia or nephrolithiasis). Moderate calcium and vitamin D intake should be maintained. In patients with concomitant vitamin D deficiency, vitamin D should be repleted carefully, to reduce the risk of worsening hypercalcemia. Serum 25(OH)D levels above 50 nmol/L are recommended, although the optimal vitamin D level for patients with PHPT is not known (level III evidence).6 Patients should also be advised to avoid factors that can exacerbate hypercalcemia, such as lithium or hydrochlorothiazide therapy, immobilization, and intravascular volume depletion.

Notes

KEY POINTS

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia in the outpatient clinical setting. There are no specific physical findings in PHPT, and parathyroid adenomas or carcinomas are rarely palpable; however, it is important to exclude neck masses. Definitive therapy for PHPT is a parathyroidectomy. For asymptomatic PHPT not meeting criteria for surgery, monitoring is a suitable option. Medical management targeting skeletal protection or lowering serum calcium can be useful in those with contraindications to, or who do not wish to have, surgery. In the absence of nephrolithiasis, a 24-hour urine calcium above 10 mmol/d is no longer an indication for parathyroidectomy, as urinary calcium excretion is affected by other factors.

POINTS DE REPÈRE

L’hyperparathyroïdie primaire (HPTP) est la cause la plus fréquente d’hypercalcémie chez les patients en consultation externe. Il n’y a pas de signe clinique spécifique à l’HPTP et les adénomes ou carcinomes parathyroïdiens sont rarement palpables; néanmoins, il est important d’exclure toute masse cervicale. Le traitement définitif de l’HPTP est la parathyroìdectomie. Pour l’HPTP asymptomatique qui ne répond pas aux critères chirurgicaux, le monitorage est une option acceptable. Un traitement médical visant à protéger le calcium osseux ou à abaisser le calcium sérique peut être utile chez les patients qui présentent des contre-indications à la chirurgie ou qui ne veulent pas être opérés. En absence de néphrolithiase, une quantité de calcium supérieure à 10 mmol/d dans l’urine de 24 heures n’est plus une indication pour une parathyroïdectomie, puisque l’excrétion urinaire du calcium est affectée par d’autres facteurs.

Levels of evidence

Level I: At least one properly conducted randomized controlled trial, systematic review, or meta-analysis

Level II: Other comparison trials, non-randomized, cohort, case-control, or epidemiologic studies, and preferably more than one study

Level III: Expert opinion or consensus statements

Footnotes

  • This article has been peer reviewed.

  • Cet article a fait l’objet d’une révision par des pairs.

  • This article is eligible for Mainpro-M1 credits. To earn credits, go to www.cfp.ca and click on the Mainpro link.

  • Contributors

    Both authors contributed to the literature review and preparing the article for submission.

  • Competing interests

    None declared

  • Copyright© the College of Family Physicians of Canada

References

  1. 1.↵
    1. Khan AA,
    2. Bilezikian JP,
    3. Potts JT Jr.,
    4. Guest Editors for the Third International Workshop on Asymptomatic Primary Hyperparathyroidism
    . The diagnosis and management of asymptomatic primary hyperparathyroidism revisited. J Clin Endocrinol Metab 2009;94(2):333-4.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Silverberg SJ,
    2. Bilezikian JP
    . Evaluation and management of primary hyperparathyroidism. J Clin Endocrinol Metab 1996;81(6):2036-40.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Khan A,
    2. Bilezikian J
    . Primary hyperparathyroidism: pathophysiology and impact on bone. CMAJ 2000;163(2):184-7.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Ruda JM,
    2. Hollenbeak CS,
    3. Stack BC Jr.
    . A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg 2005;132(3):359-72.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Souza ER,
    2. Scrignoli JA,
    3. Bezerra FC,
    4. Ribeiro SL,
    5. Passos LF
    . Devastating skeletal effects of delayed diagnosis of complicated primary hyperparathyroidism because of ectopic adenoma. J Clin Rheumatol 2008;14(5):281-4.
    OpenUrlPubMed
  6. 6.↵
    1. Eastell R,
    2. Arnold A,
    3. Brandi ML,
    4. Brown EM,
    5. D’Amour P,
    6. Hanley DA,
    7. et al
    . Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab 2009;94(2):340-50.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Tfelt-Hansen J,
    2. Brown EM
    . The calcium-sensing receptor in normal physiology and pathophysiology: a review. Crit Rev Clin Lab Sci 2005;42(1):35-70.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Cetani F,
    2. Pardi E,
    3. Borsari S,
    4. Viacava P,
    5. Dipollina G,
    6. Cianferotti L,
    7. et al
    . Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab 2004;89(11):5583-91.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Teh BT,
    2. Farnebo F,
    3. Kristoffersson U,
    4. Sundelin B,
    5. Cardinal J,
    6. Axelson R,
    7. et al
    . Autosomal dominant primary hyperparathyroidism and jaw tumor syndrome associated with renal hamartomas and cystic kidney disease: linkage to 1q21–q32 and loss of the wild type allele in renal hamartomas. J Clin Endocrinol Metab 1996;81(12):4204-11.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Wermers RA,
    2. Kearns AE,
    3. Jenkins GD,
    4. Melton LJ 3rd.
    . Incidence and clinical spectrum of thiazide-associated hypercalcemia. Am J Med 2007;120(10):911, e9-15. Epub 2007 Apr 16.
    OpenUrlCrossRef
  11. 11.↵
    1. Haden ST,
    2. Stoll AT,
    3. McCormick S,
    4. Scott J,
    5. Fuleihan G el-H
    . Alterations in parathyroid hormone dynamics in lithium-treated subjects. J Clin Endocrinol Metab 1997;82(9):2844-8.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Beard CM,
    2. Heath H 3rd.,
    3. O’Fallon WM,
    4. Anderson JA,
    5. Earle JD,
    6. Melton LJ 3rd.
    . Therapeutic radiation and hyperparathyroidism. A case-control study in Rochester, Minn. Arch Intern Med 1989;149(8):1887-90.
    OpenUrlCrossRefPubMed
  13. 13.↵
    1. Schneider AB,
    2. Gierlowski TC,
    3. Shore-Freedman E,
    4. Stovall M,
    5. Ron E,
    6. Lubin J
    . Dose-response relationships for radiation-induced hyperparathyroidism. J Clin Endocrinol Metab 1995;80(1):254-7.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Mishra SK,
    2. Agarwal G,
    3. Kar DK,
    4. Gupta SK,
    5. Mithal A,
    6. Rastad J
    . Unique clinical characteristics of primary hyperparathyroidism in India. Br J Surg 2001;88(5):708-14.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Carroll MF,
    2. Schade DS
    . A practical approach to hypercalcemia. Am Fam Physician 2003;67(9):1959-66.
    OpenUrlPubMed
  16. 16.↵
    1. Rao DS,
    2. Phillips ER,
    3. Divine GW,
    4. Talpos GB
    . Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic primary hyperparathyroidism. J Clin Endocrinol Metab 2004;89(11):5415-22.
    OpenUrlCrossRefPubMed
  17. 17.
    1. Bollerslev J,
    2. Jansson S,
    3. Mollerup CL,
    4. Nordenström J,
    5. Lundgren E,
    6. Tørring O,
    7. et al
    . Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial. J Clin Endocrinol Metab 2007;92(5):1687-92. Epub 2007 Feb 6.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Ambrogini E,
    2. Cetani F,
    3. Cianferotti L,
    4. Vignali E,
    5. Banti C,
    6. Viccica G,
    7. et al
    . Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial. J Clin Endocrinol Metab 2007;92(8):3114-21. Epub 2007 May 29.
    OpenUrlCrossRefPubMed
  19. 19.↵
    1. Helliwell M
    . Rheumatic symptoms in primary hyperparathyroidism. Postgrad Med J 1983;59(690):236-40.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    1. Silverberg SJ,
    2. Lewiecki EM,
    3. Mosekilde L,
    4. Peacock M,
    5. Rubin MR
    . Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab 2009;94(2):351-65.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Jebasingh F,
    2. Jacob JJ,
    3. Shah A,
    4. Paul TV,
    5. Seshadri MS
    . Bilateral maxillary brown tumours as the first presentation of primary hyperparathyroidism. Oral Maxillofac Surg 2008;12(2):97-100.
    OpenUrlCrossRefPubMed
  22. 22.↵
    1. Erem C,
    2. Hacihasanoglu A,
    3. Cinel A,
    4. Ersöz HO,
    5. Reis A,
    6. Sari A,
    7. et al
    . Sphenoid sinus brown tumour, a mass lesion of occipital bone and hypercalcemia: an unusual presentation of primary hyperparathyroidism. J Endocrinol Invest 2004;27(4):366-9.
    OpenUrlPubMed
  23. 23.↵
    1. Fouda MA
    . Primary hyperparathyroidism: King Khalid University Hospital experience. Ann Saudi Med 1999;19(2):110-5.
    OpenUrlPubMed
  24. 24.↵
    1. Lowe H,
    2. McMahon DJ,
    3. Rubin MR,
    4. Bilezikian JP,
    5. Silverberg SJ
    . Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype. J Clin Endocrinol Metab 2007;92(8):3001-5. Epub 2007 May 29.
    OpenUrlCrossRefPubMed
  25. 25.↵
    1. Lundgren E,
    2. Hagström EG,
    3. Lundin J,
    4. Winnerbäck K,
    5. Roos J,
    6. Ljunghall S,
    7. et al
    . Primary hyperparathyroidism revisited in menopausal women with serum calcium in the upper normal range at population-based screening 8 years ago. World J Surg 2002;26(8):931-6. Epub 2002 June 6.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Moosgaard B,
    2. Vestergaard P,
    3. Heickendorff L,
    4. Melsen F,
    5. Christiansen P,
    6. Mosekilde L
    . Vitamin D status, seasonal variations, parathyroid adenoma weight and bone mineral density in primary hyperparathyroidism. Clin Endocrinol (Oxf) 2005;63(5):506-13.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Rao DS,
    2. Agarwal G,
    3. Talpos GB,
    4. Phillips ER,
    5. Bandeira F,
    6. Mishra SK,
    7. et al
    . Role of vitamin D and calcium nutrition in disease expression and parathyroid tumor growth in primary hyperparathyroidism: a global perspective. J Bone Miner Res 2002;17(Suppl 2):N75-80.
    OpenUrlPubMed
  28. 28.↵
    1. Consensus Development Task Force on Diagnosis and Management of Asymptomatic Primary Hyperparathyroidism
    . Asymptomatic primary hyperparathyroidism: standards and guidelines for diagnosis and management in Canada. Endocr Pract 2003;9(5):400-5.
    OpenUrlPubMed
  29. 29.↵
    1. Bilezikian JP,
    2. Khan AA,
    3. Potts JT Jr.
    . Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop. J Clin Endocrinol Metab 2009;94(2):335-9.
    OpenUrlCrossRefPubMed
  30. 30.↵
    1. Rubin MR,
    2. Bilezikian JP,
    3. McMahon DJ,
    4. Jacobs T,
    5. Shane E,
    6. Siris E,
    7. et al
    . The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J Clin Endocrinol Metab 2008;93(9):3462-70. Epub 2008 Jun 10.
    OpenUrlCrossRefPubMed
  31. 31.↵
    1. Udelsman R,
    2. Pasieka JL,
    3. Sturgeon C,
    4. Young JE,
    5. Clark OH
    . Surgery for asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab 2009;94(2):366-72.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Rossini M,
    2. Gatti D,
    3. Isaia G,
    4. Sartori L,
    5. Braga V,
    6. Adami S
    . Effects of oral alendronate in elderly patients with osteoporosis and mild primary hyperparathyroidism. J Bone Miner Res 2001;16(1):113-9.
    OpenUrlCrossRefPubMed
  33. 33.
    1. Chow CC,
    2. Chan WB,
    3. Li JK,
    4. Chan NN,
    5. Chan MH,
    6. Ko GT,
    7. et al
    . Oral alendronate increases bone mineral density in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab 2003;88(2):581-7.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Khan AA,
    2. Bilezikian JP,
    3. Kung AW,
    4. Ahmed MM,
    5. Dubois SJ,
    6. Ho AY,
    7. et al
    . Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial. J Clin Endocrinol Metab 2004;89(7):3319-25.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Grey AB,
    2. Stapleton JP,
    3. Evans MC,
    4. Tatnell MA,
    5. Reid IR
    . Effect of hormone replacement therapy on bone mineral density in postmenopausal women with mild primary hyperparathyroidism. A randomized, controlled trial. Ann Intern Med 1996;125(5):360-8.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Khan A,
    2. Grey A,
    3. Shoback D
    . Medical management of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab 2009;94(2):373-81.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Rubin MR,
    2. Lee KH,
    3. McMahon DJ,
    4. Silverberg SJ
    . Raloxifene lowers serum calcium and markers of bone turnover in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab 2003;88(3):1174-8.
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

Canadian Family Physician: 57 (2)
Canadian Family Physician
Vol. 57, Issue 2
1 Feb 2011
  • Table of Contents
  • About the Cover
  • Index by author
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on The College of Family Physicians of Canada.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Primary hyperparathyroidism
(Your Name) has sent you a message from The College of Family Physicians of Canada
(Your Name) thought you would like to see the The College of Family Physicians of Canada web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Primary hyperparathyroidism
Shelley Pallan, Aliya Khan
Canadian Family Physician Feb 2011, 57 (2) 184-189;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Share
Primary hyperparathyroidism
Shelley Pallan, Aliya Khan
Canadian Family Physician Feb 2011, 57 (2) 184-189;
Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Quality of evidence
    • Main message
    • Notes
    • Footnotes
    • References
  • Figures & Data
  • eLetters
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Bilateral pathologic mid-tibial stress fractures: Initial presentation of mild primary hyperparathyroidism
  • Same-day discharge after unilateral parathyroidectomy is safe
  • Correction
  • Bilateral neck exploration in patients with primary hyperparathyroidism and discordant imaging results: a single-centre study
  • Google Scholar

More in this TOC Section

Practice

  • Managing type 2 diabetes in primary care during COVID-19
  • Effectiveness of dermoscopy in skin cancer diagnosis
  • Spontaneous pneumothorax in children
Show more Practice

Clinical Review

  • Top studies of 2024 relevant to primary care
  • Approach to steatotic liver disease in the office
  • Foreskin care
Show more Clinical Review

Similar Articles

Navigate

  • Home
  • Current Issue
  • Archive
  • Collections - English
  • Collections - Française

For Authors

  • Authors and Reviewers
  • Submit a Manuscript
  • Permissions
  • Terms of Use

General Information

  • About CFP
  • About the CFPC
  • Advertisers
  • Careers & Locums
  • Editorial Advisory Board
  • Subscribers

Journal Services

  • Email Alerts
  • Twitter
  • LinkedIn
  • Instagram
  • RSS Feeds

Copyright © 2025 by The College of Family Physicians of Canada

Powered by HighWire