Hyperparathyroidism in Otolaryngology and Facial Plastic Surgery Workup
- Author: James LaBagnara, MD; Chief Editor: Arlen D Meyers, MD, MBA more...
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- Diagnosis is made based on hypercalcemia and elevated parathyroid hormone (PTH) levels. Other abnormal laboratory findings may include elevated BUN and creatinine levels, hyperchloremic acidosis, reduced serum bicarbonate levels due to renal bicarbonate casting, hypophosphatemia, elevated alkaline phosphatase levels and hypercalciuria.
- Other causes of hypercalcemia (eg, paraneoplastic syndromes, malignancies, Paget disease, drug-induced causes, dietary causes) are not associated with PTH level elevation. However, occasionally, primary hyperparathyroidism and malignancy-related hypercalcemia may coexist.
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- The importance of preoperative localization studies can substantially reduce operative time, cost, and patient morbidity. This is important in the era of managed care and operating room cost containment. Without preoperative localization, a parathyroid adenoma is successfully identified and removed in more than 95% of patients, although this may require exploration of all 4 glands.
- Accurate localization can limit exploration to the identified side, allowing rapid removal of the adenoma. If a second adenoma is present, both adenomas are frequently identified with preoperative ultrasonography and sestamibi scan, even if the lesion is in an ectopic location. Localization may not reduce the need for a later reexploration for a mediastinal adenoma. A list of noninvasive imaging modalities and their usefulness and ease of performance appears below, in order of increasing cost, as follows:
- High-resolution ultrasonography: In the hands of an experienced ultrasonographer, this method is the most economic and may provide maximum information. It shows enlarged parathyroid glands and their relationship to relevant neck anatomy, thyroid nodules, and lymph nodes. High-resolution ultrasonography can reveal multiple adenomas, hyperplasia of all 4 glands, and glands in ectopic cervical locations such as within the carotid sheath or thyroid. However, high-resolution ultrasonography can not identify mediastinal adenomas.
- Technetium-99m labeled sestamibi scan
- This nuclear material has a specific affinity for abnormal parathyroid tissue. Although uptake also occurs in thyroid tissue, technetium-99m rapidly diminishes in the thyroid but is retained in the parathyroid mitochondria.
- Sestamibi scan is useful in identifying single and multiple parathyroid adenomas and hyperplasia. Sestamibi also can reveal ectopic glands.
- Although sestamibi is most often used preoperatively, it can also be used intraoperatively. Intrathoracic adenomas can also be identified despite the overlying sternum. A sestamibi scan that fails to reveal an adenoma in a patient with hypercalcemia and elevated PTH levels may suggest diffuse hyperplasia of all 4 glands or the presence of an adenoma that has a cell population that consists mainly of chief cells.
- Although sestamibi is very sensitive with single adenomas, it fails to reveal 17% of second adenomas and 55% of hyperplastic glands. The outcome of the sestamibi scan is most influenced by the size of the adenoma; scans of lesions less than 2 cm in size are often difficult to interpret. Since sestamibi is concentrated in mitochondria, the sensitivity of sestamibi has histopathologic considerations that vary by the predominant cell type within the adenoma.
- Adenomas that are rich in Oxyphil cells have a higher mitochondrial content, greater metabolic activity, and increased radiotracer uptake. Adenomas that are predominantly chief cells have minimal mitochondrial content and minimal radiotracer uptake.
- CT scan: CT scanning provides excellent spatial resolution and greater detail than the images obtained in a single plane. CT scans can be reconstructed for additional views. The location of an enlarged gland can be precisely defined in relation to adjacent anatomy. CT scan is helpful in locating mediastinal adenomas as well.
- MRI: MRI provides excellent contrast resolution; images can be formatted in multiple planes (ie, axial, coronal, sagittal). Increased vascularity of the adenomas is ideal for identification with this modality. MRI may be useful in locating mediastinal adenomas.
- Combination of ultrasonography and sestamibi scan provides maximum information and is cost effective.
- CT scan or MRI for mediastinum adenomas may be required when an adenoma is suspected in the thorax.
In primary hyperparathyroidism, the adenomas represent true neoplasms. Diffuse hyperplasia occurs in the absence of an adenoma. Hyperplasia of all 4 glands is often dramatic in renal (secondary) hyperparathyroidism with significantly increased gland volumes and weights.
Frozen section differentiation of an adenoma from hyperplasia is difficult for the pathologist. In the operating room, the surgeon primarily wishes to know that the specimen contains parathyroid tissue. An adenoma can be identified on permanent section if the surrounding halo or rim of fat is visible along with certain cellular characteristics. An experienced surgeon can usually identify an adenoma in situ based on its size and color as compared with a normal parathyroid gland, lymph node, or globule of fat.
Carney JA. The glandulae parathyroideae of Ivar Sandström. Contributions from two continents. Am J Surg Pathol. 1996 Sep. 20(9):1123-44. [Medline].
Mandl F. Klinisches und experimenteles zur fraga der lakalisierten und generalisiereten osteitis fibrosa. Arch Klin Chir. 1926. 142.
Albright F, Aub J, Bauer W. Hyperparathyroidism: A common and polymorphic condition as illustrated by 17 cases from one clinic. JAMA. 1934. 102:1276.
Akhaliia MG, Meladze GD, Dzhgamadze ShV, Kakiashvili MS, Gotsiridze GSh. [New method of determining the pathophysiological changes in the pleural exudate for the diagnosis of postoperative complications]. Grudn Khir. 1975 Nov-Dec. 58-63. [Medline].
Yamamoto T, Tominaga Y, Okada M, et al. Characteristics of Persistent Hyperparathyroidism After Renal Transplantation. World J Surg. 2015 Nov 6. [Medline].
Carling T, Udelsman R. Parathyroid surgery in familial hyperparathyroid disorders. J Intern Med. 2005 Jan. 257(1):27-37. [Medline].
Hu S, Cai X, Mewani V, Trooskin S, Wang X. Impact of ethnic background on clinical characteristics and cardiovascular risk factors among patients with primary hyperparathyroidism. Endocr Pract. 2015 Nov 4. [Medline].
Maruani G, Hertig A, Paillard M, Houillier P. Normocalcemic primary hyperparathyroidism: evidence for a generalized target-tissue resistance to parathyroid hormone. J Clin Endocrinol Metab. 2003 Oct. 88(10):4641-8. [Medline].
NIH conference. Diagnosis and management of asymptomatic primary hyperparathyroidism: consensus development conference statement. Ann Intern Med. 1991 Apr 1. 114(7):593-7. [Medline].
Harrison P. Surgery Better Than Cinacalcet for Hyperparathyroidism. Medscape Medical News. Jun 16, 2015. [Full Text].
Isaacks RE, Harkness DR, Froeman GA, Sussman SA. Studies on avian erythrocyte metabolism--I. Procedure for separation and quantitation of the major phosphorylated metabolic intermediates by anion exchange chromatography. Comp Biochem Physiol A Comp Physiol. 1976 Jan. 53(1):95-9. [Medline].
Vasher M, Goodman A, Politz D, Norman J. Postoperative calcium requirements in 6,000 patients undergoing outpatient parathyroidectomy: easily avoiding symptomatic hypocalcemia. J Am Coll Surg. 2010 Jul. 211(1):49-54. [Medline].
Norman J, Politz D. Prospective Study in 3,000 Consecutive Parathyroid Operations Demonstrates 18 Objective Factors that Influence the Decision for Unilateral versus Bilateral Surgical Approach. jamcollsurg. aug/2010. 211 2:1072-7515/10.
Dogan R, Kara M, Yazicioglu A, Kaynaroglu V. The use of gamma probe for the intraoperative localization of an ectopic parathyroid adenoma. Tuberk Toraks. 2009. 57(2):208-11. [Medline].
Tolley N, Arora A, Palazzo F, et al. Robotic-assisted parathyroidectomy: a feasibility study. Otolaryngol Head Neck Surg. 2011 Jun. 144(6):859-66. [Medline].
Albright F. Page out of the history of hyperparathyroidism. J Clin Endocrinol. 1948. 8:637.
Albright F, Butler A, Hampton A. Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females. N Engl J Med. 1937. 216:727-746.
B. Dijkstra, C. Healy, L.M. Kelly, E.W. McDermott, A.D.K. Hill, N. O'Higgins. Clinical review: Parathyroid Localization-current practice. J.R.Coll.Edinb. Aug 2002. 47:599-607.
Brenner BM, Rector FC. Brenner & Rector's The Kidney. 5th ed. Philadelphia:. WB Saunders Co. 1996.
Cecil RL, Bennett JC, Plum F. Cecil Textbook of Medicine. 20th ed. Philadelphia: WB Saunders Co. 1996.
Cecil RL, Smith LH, Wyngaarden JB. Cecil Review of General Internal Medicine. 3rd ed. Philadelphia: WB Saunders Co. 1985.
Clark O. Endocrine surgery of the thyroid and parathyroid glands. In: Endocrine Surgery. 1985.
Díaz-Aguirregoitia FJ, Emparan C, Gaztambide S, Aniel-Quiroga MA, Busturia MA, Vázquez JA, et al. Intraoperative monitoring of kinetic total serum calcium levels in primary hyperparathyroidism surgery. J Am Coll Surg. 2004 Apr. 198(4):519-24. [Medline].
Ehrig U, Wilson DR. Fibrous dysplasia of bone and primary hyperparathyroidism. Ann Intern Med. 1972 Aug. 77(2):234-8. [Medline].
Fraker DL, Travis WD, Merendino JJ Jr, et al. Locally recurrent parathyroid neoplasms as a cause for recurrent and persistent primary hyperparathyroidism. Ann Surg. 1991 Jan. 213(1):58-65. [Medline].
Gates G. Current Therapy in Otolaryngology-Head and Neck Surgery. 5th ed. Mosby-Year Book. 1990.
Greenberg CC, Regenbogen SE, Studdert DM, et al. Patterns of communication breakdowns resulting in injury to surgical patients. J Am Coll Surg. 2007 Apr. 204(4):533-40. [Medline].
Kellett HA, MacLaren IF, Toft AD. Gout and pseudogout precipitated by parathyroidectomy. Scott Med J. 1982 Jul. 27(3):250-1. [Medline].
LaBagnara J Jr, Yuppa F, Klein MH. Fibrous dysplasia of the middle turbinate with primary hyperparathyroidism. Ear Nose Throat J. 1998 Jul. 77(7):552-3. [Medline].
Lairmore TC, Howe JR, Korte JA, et al. Familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2B map to the same region of chromosome 10 as multiple endocrine neoplasia type 2A. Genomics. 1991 Jan. 9(1):181-92. [Medline].
Larsson C, Skogseid B, Oberg K, et al. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature. 1988 Mar 3. 332(6159):85-7. [Medline].
Marx SJ, Simonds WF, Agarwal SK, et al. Hyperparathyroidism in hereditary Syndromes: special expressions and special managements. J Bone Miner Res. 2002 Nov. 17 Suppl 2:N37-43. [Medline].
Marx SJ, Spiegel AM, Levine MA, et al. Familial hypocalciuric hypercalcemia: the relation to primary parathyroid hyperplasia. N Engl J Med. 1982 Aug 12. 307(7):416-26. [Medline].
McBiles M, Lambert AT, Cote MG, Kim SY. Sestamibi parathyroid imaging. Semin Nucl Med. 1995 Jul. 25(3):221-34. [Medline].
Mehta NY, Ruda JM, Kapadia S, Boyer PJ, Hollenbeak CS, Stack BC Jr. Relationship of technetium Tc 99m sestamibi scans to histopathological features of hyperfunctioning parathyroid tissue. Arch Otolaryngol Head Neck Surg. 2005 Jun. 131(6):493-8. [Medline].
Norman J, Aronson K. Outpatient parathyroid surgery and the differences seen in the morbidly obese. Otolaryngol Head Neck Surg. 2007 Feb. 136(2):282-6. [Medline].
Pattou F, Huglo D, Proye C. Radionuclide scanning in parathyroid diseases. Br J Surg. 1998 Dec. 85(12):1605-16. [Medline].
Prekeges JL, Eisenberg B. Parathyroid scintigraphy. J Nucl Med Technol. 1997 Mar. 25(1):59-65. [Medline].
Rogers H. Primary hyperparathyroidism and hyperplasia of parathyroid glands associated with duodenal ulcer: report of an additional case with special reference to metabolic, gastrointestinal and vascular manifestations. Arch Int Med. 1947. 79:3-7.
Schwartz SI. Principles of Surgery. 7th ed. McGraw-Hill. 1999.
Soon PS, Yeh MW, Sywak MS, Roach P, Delbridge LW, Sidhu SB. Minimally invasive parathyroidectomy using the lateral focused miniincision approach: Is there a learning curve for surgeons experienced in the open procedure?. J Am Coll Surg. 2007 Jan. 204(1):91-5. [Medline].
|Disorder||Inheritance||Gene||Chromosome||Penetrance and Findings||Associated|
|RET||10q21||Low penetrance, (approximately 20%),|
usually single adenoma,
may be multiglandular
tumors, 15% risk of CA
|Jaw tumors, renal|
|3q13-q21||Mildly hyperplastic||Mildest form of|
|3q13-q21||Markedly hyperplastic||Severest form of|
very high PTH level,
|Disorder||Dominant Feature||Treatment||Notable Facts|
|Total parathyroidectomy with search|
|MEN2A||Medullary carcinoma||Removal of single|
glands left in situ
cystic parathyroid tumors
(may reduce risk of cancer)
|Only 30 families|
reported; 15% risk of
Single adenoma treated with resection;
multiglandular disease treated with subtotal parathyroidectomy
|Linked to MEN1 gene,|
HRPT gene and CASR
|ADMH||...||Subtotal parathyroidectomy||CASR mutation|
hypercalcemia at birth but little long-term
|No benefit from|
of mildly enlarged
glands; total parathyroidectomy with autotransplantation for severe forms
|NSHPT||Very high PTH level, severe|
|Total parathyroidectomy within first|
months of life (condition often lethal)