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Management of Parathyroid.pptx
- 1. Management of Parathyroid Diseases By- Weini Tekle PGYIII Moderator – Dr. Endale Anberbir Consultant General, endocrine and breast surgeon 1
- 2. Hyperparathyroidism • Hyperfunction of the parathyroid glands • classified as • primary, • Secondary • tertiary. 2
- 3. Primary hyperparathyroidism (PHPT) • occurs in 0.1% to 0.3% of the general population • Women account ¾ of all cases • Peak at 7th decade of life • leads to hypercalcemia via increased GI absorption of calcium, increased production of vitamin D3, and reduced renal calcium clearance. • characterized by increased parathyroid cell proliferation and PTH secretion that is independent of calcium levels. 3
- 4. Etiology • exposure to low-dose therapeutic ionizing radiation – latency period 30 to 40 years • Higher PTH and concomitant thyroid neoplasms • familial predisposition • renal leak of calcium • declining renal function with age • alteration in the sensitivity of parathyroid glands to suppression by calcium. 4
- 5. Genetics • Most cases of PHPT are sporadic. • also occurs within the spectrum of a number of inherited disorders such as • MEN1, MEN2A, isolated familial HPT, and familial HPT with jaw-tumor syndrome. • All of these syndromes are inherited in an autosomal dominant fashion. 5
- 6. MEN 1 • typically - parathyroid, pancreatic islet, and anterior pituitary • neuroendocrine tumors of the thymus, bronchus or stomach, adrenal adenomas, lipomas, and axillary skin tags. • 1-18% of patients with pHPT have MEN1 • the penetrance of parathyroid disease in patients with MEN1 is >95% • typically present with parathyroid disease in the third decade • About 50% of patients develop gastrinomas • Insulinomas develop in 10% to 15% of cases • Prolactinomas occur in 10% to 50% of MEN1 6
- 7. MEN 2A • medullary carcinoma of the thyroid, pheochromocytoma, parathyroid hyperplasia or adenomas, occasionally cutaneous lichen amyloidosis. • pHPT has a penetrance of 15-30%, • >90% for medullary thyroid cancer • 40-50% for pheochromocytoma 7
- 8. Hyperparathyroidism – Jaw Tumor Syndrome (HPT-JT) • an autosomal dominant disorder, • characterized by both benign and malignant parathyroid disease, fibromas of the mandible and maxilla, renal tumors, and uterine tumors. • The average age of onset is not well-established, • a median age of diagnosis of pHPT in the second or third decade 8
- 9. Clinical manifestations • The pentad of symptoms—painful bones, kidney stones, abdominal groans, psychic moans, and fatigue overtones • most patients present with weakness, fatigue, polydipsia, polyuria, nocturia, bone and joint pain, constipation, decreased appetite, nausea, heartburn, pruritus, depression, and memory loss. • these symptoms and signs improve in most, but certainly not all, patients after parathyroidectomy. • Truly “asymptomatic” PHPT appears to be rare, occurring in <5% of patients, 9
- 10. Complications - Renal Disease • ∼ 80% of patients • Kidney stones – • Nephrocalcinosis, <5% • Chronic hypercalcemia - • impair concentrating ability. • hypertension - occur in up to 50% of patients • is least likely to improve after parathyroidectomy. 10
- 11. Bone Disease • osteopenia, osteoporosis, and osteitis fibrosa cystica, is found in about 15% of patients • Increased bone turnover - elevated blood ALP level. • It has pathognomonic radiologic findings, • reductions of bone mineral density (BMD) • Bone disease correlates with serum PTH and vitamin D levels. 11
- 12. Gastrointestinal Complications. • peptic ulcer disease. • pancreatitis - (Ca2+ ≥12.5 mg/dL). • Cholelithiasis •Neuropsychiatric Complications. • Severe hypercalcemia - florid psychosis, obtundation, or coma • mild hypercalcemia - depression, anxiety, and fatigue • EEG changes. 12
- 13. Other Features. • fatigue and muscle weakness, • chondrocalcinosis, gout, and pseudogout, • Calcification at blood vessels, cardiac valves, and skin • LVH independent of the presence of hypertension. • increased death rates from cardiovascular disease and cancer 13
- 14. Physical Findings • seldom palpable, except in patients with profound hypercalcemia or parathyroid cancer. • A palpable neck mass in a patient with PHPT is more likely to be thyroid in origin or a parathyroid cancer. • Patients also may demonstrate evidence of band keratopathy, • a deposition of calcium in Bowman’s membrane just inside the iris of the eye • Fibro-osseous jaw tumors, and/or the presence of familial disease in patients with PHPT and jaw tumors, if present, should alert the physician to the possibility of parathyroid carcinoma. 14
- 15. 15
- 16. Work up - Biochemical studies • total calcium, • PTH, • creatinine, • 25-OH vitamin D levels • A 24-hour urine measurement of calcium and creatinine • Cccr <0.01 = FHH , Cccr >0.02 = PHPT • Abdominal u/s • Bone density examination - DXA 16
- 17. Genetic counselling/ screening • patients <40 years of age with PHPT • MEN 1 - < 30 years – test MEN 1 gene mutation, age of 10 years • MEN 2A –test RET mutation • screening surveillance for pHPT should be performed annually with albumin- corrected calcium • age of 11 – 16 yrs • HPT-JT – test for CDC73 • all patients with parathyroid carcinoma, and when MEN1 mutation analysis is negative • multigland disease (MGD), • a family history or • syndromic manifestations 17
- 18. 18
- 19. Treatment • If complication or classical symptoms – parathyroidectomy • If asymptomatic – controversial • Non-operative/ operative – disease progression and end organ effect • Medical options • Bisphosphonates • HRT • selective estrogen receptor modulators - raloxifene • Calcimimetics – modifiers of sensitivity of CaSR - ↓ PTH and Ca Skeletal protection/ ↑BMD 19
- 20. Parathyroidectomy • resolution of osteitis fibrosa cystica • decreased formation of renal stones • improved BMD (6% to 8% in the first year and up to 12% to 15% at 15 years) • fracture risk (by 50% at hip and upper arm and 30% overall) • improves a number of the nonspecific manifestations of PHPT such as fatigue, polydipsia, polyuria and nocturia, bone and joint pain, constipation, nausea, and depression in many patients. • Reverses The increased death • can be accomplished with >95% success rates with minimal morbidity • is the only curative treatment option for PHPT. Previous investigations have also documented that parathyroidectomy is more cost-effective than medical management or follow-up. 20
- 21. Preoperative Localization Tests • Allow for limited surgery • Non-invasive • u/s – 76% sn, 93% PPV • Sestamibi-technetium- 99m scan 61-100% • PET scan – sn 86% sp 78% • CT scan – sn (40–66%) sp. (88–89%) • MRI sn 43-82% 21
- 22. Invasive localization tests • preop • Reserved for remedial surgeries • Catheter-based localization with arteriography • venous sampling • PTH assay • FNAB • Intraop • Radio-guided surgery • Intraop u/s • Parathyroid aspiration +/- rapid PTH assay • IOPTH measurement • Bilateral jugular vein sampling • Methylene blue 22
- 23. Unilateral neck exploration • advantages - reduced operative times • Reduced complications, such as injury to the RLN and hypoparathyroidism • Initially, the choice of side to be explored was random, • introduction of preoperative localization studies has enabled a more directed approach • risk of missing another adenoma on the opposite side of the neck • incidence of double adenomas - 0% to 10%, • increased incidence in elderly patients 23
- 24. Bilateral neck exploration • It is planned: • If parathyroid localization studies are not available • If the localizing studies fail to identify any abnormal parathyroid gland • Fail to identify multiple abnormal glands in patients with a family history of PHPT, MEN1, or MEN2A • If a concomitant thyroid disorder requires bilateral exploration 24
- 25. • 80% of patients with PHPT - A single adenoma is presumed to be the cause • 10% of patients Multiple adenomas (double or tirple) - >60 years old • 15% of patients - If all parathyroid glands are enlarged or hypercellular, patients have parathyroid hyperplasia • subtotal parathyroidectomy or by total parathyroidectomy and autotransplantation • Autotransplanted tissue may fail to function in about 5% of cases 25
- 26. Conduct of parathyroidectomy • 85% of the parathyroid glands are found within 1 cm of the junction of the inferior thyroid artery and RLNs • Normal parathyroids are light beige and only slightly darker or brown compared to adjacent fat • size (>7 mm), color, and weight are used to distinguish normal from hypercellular parathyroid glands • Hypercellular glands generally are darker, more firm, and more vascular than normocellular glands 26
- 27. Post op followup • calcium level - 2 weeks postoperatively, at 6 months, and then annually. • Recurrences -(<1%), 15% at 2 years and 67% at 8 years for MEN1 patients. • persistence - hypercalcemia that fails to resolve after parathyroidectomy • Recurrence - HPT occurring after an intervening period of at least 6 months of biochemically documented normocalcemia. 27
- 28. • Causes – • ectopic parathyroids, • unrecognized hyperplasia, • supernumerary glands. • parathyroid carcinoma, • missed adenoma in a normal position, • incomplete resection of an abnormal gland, • parathyromatosis, • inexperienced surgeon. 28
- 29. • lateral approach is frequently used via the previous incision. • The plane between the sternocleidomastoid and strap muscle is opened • Parathyroid tissue is cryopreserved routinely. • measuring intraoperative PTH levels, to ensure adequate • In case of difficult reexplorations, • bilateral internal jugular vein sampling for PTH, • thyroid lobectomy on the side of the missing gland, • cervical thymectomy, and • ligation of the ipsilateral inferior thyroid artery • Blind mediastinal exploration is not recommended. • medical options such as cinacalcet may be considered. 29
- 30. Parathyroid ca • 1% of PHPT cases. • Suspect if severe symptoms, serum calcium levels >14 mg/dL, significantly elevated PTH levels (five times normal), and a palpable parathyroid gland. • Local invasion - common; • 15% of patients have LN metastases, 33% have distant metastases at presentation. • Intraoperatively, a large, gray-white to gray-brown parathyroid tumor that is adherent • Accurate diagnosis - histologic examination. • The major diagnostic criteria include vascular or capsular invasion, trabecular or fibrous stroma, and frequent mitoses 30
- 31. Tx • neck exploration, + en bloc excision of the tumor + the ipsilateral thyroid lobe, • removal of contiguous lymph nodes (tracheoesophageal, paratracheal, and upper mediastinal). • Adherent soft tissue structures (strap muscles or other soft tissues) should also be resected. • The recurrent nerve is not sacrificed unless it is directly involved with tumor. • Modified radical neck dissection is recommended in the presence of lateral lymph node metastases. • Prophylactic neck dissection is not advised 31
- 32. • Reoperation - locally recurrent or metastatic disease to control hypercalcemia. • Adjuvant for high risk of local recurrence • positive margins, invasion of surrounding structures, or tumor rupture. • in unresectable disease • for palliation of bone metastases. • Chemotherapy is not very effective. • Bisphosphonates to treat hypercalcemia • Cinacalcet hydrochloride, a calcimimetic, can reduce PTH levels for pts with refractory parathyroid carcinoma. 32
- 33. Secondary hyperparathyroidism • chronic renal failure , inadequate calcium or vitamin D intake or malabsorption • hypocalcemic or normocalcemic • low 1,25-dihydroxyvitamin D and hyperphosphatemia • Tx- medical low-phosphate diet, phosphate binders, adequate intake of calcium and vitamin D, and a high-calcium, low-aluminum dialysis bath • Calcimimetics 33
- 34. Indication for surgery Calcium-to-phosphorous product >7 Serum calcium >11.5 mg/dl Symptoms of bone pain and pruritus Osteitis fibrosa cystica Tumoral calcinosis Calciphylaxis 34
- 35. Tertiary Hyperparathyroidism • PTH, calcium, and phosphorus levels are elevated • Tertiary HPT can cause problems similar to PHPT, • The transplanted kidney is also at risk from tubulointerstitial calcification and volume depletion • Treatment - cinacalcet (a calcimimetic) • Parathyroidectomy Indications • Autonomous PTH secretion persisting for >1 year after a successful transplant in patients with hypophosphatemia • Low BMD/severe osteopenia • Symptoms and signs such as fatigue, pruritis, bone pain, PUD or nephrocalcinosis 35
- 36. Other parathyroid disorders • Hypoparathyroidism • Congenital hypoparathyroidism – DiGeorge syndrome or 2ry • Pseudohypoparathyroidism • Tx- oral calcium and vitamin D supplements 36
- 37. References Schwartz's principle of surgery, 11th edition Electron Kebebew Endocrine Surgery (2016) Sabiston text book of Surgery, 20th edition Orlo H Clark, Textbook of Endocrine Surgery, 3rd edition • Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. Published online August 10, 2016. doi:10.1001/jamasurg.2016.2310. • International Journal of Endocrinology/2020 • Jornal of clinical endocrinology and metabolism 37
Editor's Notes
- PHPT arises from increased PTH production from abnormal parathyroid glands and results from a disturbance of normal feedback control exerted by serum calcium. Elevated PTH levels may also occur as a compensatory response to hypocalcemic states resulting from chronic renal failure or GI malabsorption of calcium. This secondary HPT can be reversed by correction of the underlying problem (e.g., kidney transplantation for chronic renal failure). However, chronically stimulated glands may occasionally become autonomous, resulting in persistence or recurrence of hypercalcemia after successful renal transplantation, resulting in tertiary HPT.
- The exact cause of PHPT is unknown, although exposure to low-dose therapeutic ionizing radiation and familial predisposition account for some cases. Various diets and intermittent exposure to sunshine may also be related. Other causes include renal leak of calcium and declining renal function with age as well as alteration in the sensitivity of parathyroid glands to suppression by calcium. The latency period for development of PHPT after radiation exposure is longer than that for the development of thyroid tumors, with most cases occurring 30 to 40 years after exposure. Patients who have been exposed to radiation have similar clinical presentations and calcium levels when compared to patients without a history of radiation exposure. However, the former tends to have higher PTH levels and a higher incidence of concomitant thyroid neoplasms.
- Most cases of PHPT are sporadic. However, PHPT also occurs within the spectrum of a number of inherited disorders such as MEN1, MEN2A, isolated familial HPT, and familial HPT with jaw-tumor syndrome. All of these syndromes are inherited in an autosomal dominant fashion. PHPT is the earliest and most common manifestation of MEN1 and develops in 80% to 100% of patients by age 40 years old. These patients also are prone to pancreatic neuroendocrine tumors and pituitary adenomas and, less commonly, to adrenocortical tumors, lipomas, skin angiomas, and carcinoid tumors of the bronchus, thymus, or stomach. About 50% of patients develop gastrinomas, which often are multiple and metastatic at diagnosis. Insulinomas develop in 10% to 15% of cases, whereas many patients have nonfunctional pancreatic endocrine tumors. Prolactinomas occur in 10% to 50% of MEN1 patients and constitute the most common pituitary lesion. MEN1 has been shown to result from germline mutations in the MEN1 gene, a tumor suppressor gene located on chromosome 11q12-13 that encodes menin, a protein that is postulated to interact with the transcription factors JunD and nuclear factor-κB in the nucleus, in addition to replication
- only symptoms of fatigue, bone pain, and weight loss seemed to correlate with the severity of hypercalcemia
- Renal Disease. Approximately 80% of patients with PHPT have some degree of renal dysfunction or symptoms. Kidney stones were previously reported in up to 80% of patients but now occur in about 20% to 25%. The calculi are typically composed of calcium phosphate or oxalate. In contrast, PHPT is found to be the underlying disorder in only 3% of patients presenting with nephrolithiasis. Nephrocalcinosis, which refers to renal parenchymal calcification, is found in <5% of patients and is more likely to lead to renal dysfunction. Chronic hypercalcemia also can impair concentrating ability, thereby resulting in polyuria, polydipsia, and nocturia. The incidence of hypertension is variable but has been reported to occur in up to 50% of patients with PHPT. Hypertension appears to be more common in older patients and correlates with the magnitude of renal dysfunction and, in contrast to other symptoms, is least likely to improve after parathyroidectomy.
- . Bone disease, including osteopenia, osteoporosis, and osteitis fibrosa cystica, is found in about 15% of patients with PHPT. Increased bone turnover, as found in patients with osteitis fibrosa cystica, can be determined by documenting an elevated blood alkaline phosphatase level. Advanced PHPT with osteitis fibrosa cystica now occurs in <5% of patients. It has pathognomonic radiologic findings, which are best seen on X-rays of the hands and are characterized by subperiosteal resorption (most apparent on the radial aspect of the middle phalanx of the second and third fingers), bone cysts, and tufting of the distal phalanges (Fig. 38-29). The skull also may be affected and appears mottled with a loss of definition of the inner and outer cortices. Brown or osteoclastic tumors and bone cysts also may be present. Severe bone disease, resulting in bone pain and tenderness and/or pathologic fractures, is rarely observed nowadays. However, reductions of bone mineral density (BMD) with osteopenia and osteoporosis are more common. Patients with normal serum alkaline phosphatase levels almost never have clinically apparent osteitis fibrosa cystica. HPT typically results in a loss of bone mass at sites of cortical bone such as the radius and relative preservation of cancellous bone such as that located at the vertebral bodies. Patients with PHPT, however, also may have osteoporosis of the lumbar spine that improves dramatically following parathyroidectomy. Fractures also occur more frequently in patients with PHPT, and the incidence of fractures also decreases after parathyroidectomy. Bone disease correlates with serum PTH and vitamin D levels.
- Gastrointestinal Complications. PHPT has been associated with peptic ulcer disease. In experimental animals, hypergastrinemia has been shown to result from PTH infusion into blood vessels supplying the stomach, independent of its effects on serum calcium. An increased incidence of pancreatitis also has been reported in patients with PHPT, although this appears to occur only in patients with profound hypercalcemia (Ca2+ ≥12.5 mg/dL). Patients with PHPT also have an increased incidence of cholelithiasis, presumably due to an increase in biliary calcium, which leads to the formation of calcium bilirubinate stones.
- Other Features. PHPT also can lead to fatigue and muscle weakness, which is prominent in the proximal muscle groups. Although the exact etiology of this finding is not known, muscle biopsy studies show that weakness results from a neuropathy, rather than a primary myopathic abnormality. Patients with HPT also have an increased incidence of chondrocalcinosis, gout, and pseudogout, with deposition of uric acid and calcium pyrophosphate crystals in the joints. Calcification at ectopic sites such as blood vessels, cardiac valves, and skin also has been reported, as has hypertrophy of the left ventricle independent of the presence of hypertension. There is also evidence for subtle cardiovascular manifestations in mild disease, such as changes in endothelial function, increased vascular stiffness, and perhaps subtle diastolic dysfunction. Several large studies from Europe also suggest that PHPT is associated with increased death rates from cardiovascular disease and cancer even in patients with mild HPT, although this finding was not substantiated in North American studies.
- Biochemical studies The presence of an elevated serum calcium and intact PTH or two-site PTH levels, without hypocalciuria, establishes the diagnosis of PHPT with virtual certainty Occasionally, patients present with normocalcemic PHPT due to vitamin D deficiency, a low serum albumin, excessive hydration, a high-phosphate diet, or a low normal blood calcium set point Patients with PHPT typically have decreased serum phosphate (∼50%) and elevated 24-hour urinary calcium concentrations (∼60%) A mild hyperchloremic metabolic acidosis also is present (80%), thereby leading to an elevated chloride-to-phosphate ratio (>33) Elevated levels of ALP may be found in approximately 10% of patients with PHPT and are indicative of high-turnover bone disease These patients are prone to developing postoperative hypocalcemia due to bone hunger
- 3
- At the National Institutes of Health consensus conference in 1990, “asymptomatic” PHPT was defined as “the absence of common symptoms and signs of PHPT, including no bone, renal, gastrointestinal, or neuromuscular disorders.” To determine the best course of action for these patients, it is important to consider the natural history of untreated PHPT and the outcomes of treatment options, both medical and surgical. Operative – if any sign of end organ effects and likelihood of disease progression best predictor is age <50 However, the long-term study suggested that the stability was not indefinite as calcium levels tended to rise in years 13 to 15. In addition, the study also demonstrated that bone density measurements remained stable for 8 to 10 years, but cortical bone density worsened after year 10. More concerning was the fact that 60% of patients lost >10% of their BMD over the 15-year observation period. Furthermore, whether patients met the 2002 guidelines for surgery did not appear to predict the risk of progressive disease, with 40% of patients undergoing follow-up eventually needing surgery. Although there are no randomized trials, registry data also suggest that fracture risk is increased for PHPT up to 10 years prior to diagnosis and treatment. Antiresorptive – bisphosphonate, HRT, Raloxifne
- Successful parathyroidectomy results in resolution of osteitis fibrosa cystica and decreased formation of renal stones in symptomatic (classic) patients. In addition, it results in improved BMD (6% to 8% in the first year and up to 12% to 15% at 15 years) and fracture risk (by 50% at hip and upper arm and 30% overall) after adjustment for age, sex, and previous fractures over a 20-year observation period.75 There are also data to show that it improves a number of the nonspecific manifestations of PHPT such as fatigue, polydipsia, polyuria and nocturia, bone and joint pain, constipation, nausea, and depression in many patients. This also has been demonstrated using symptom questionnaires and various standardized general quality-of-life assessments such as the SF-36 and a specific parathyroidectomy assessment of symptoms scale.79 The increased death rate in patients with PHPT appears to be reversible by successful parathyroidectomy, at least in some studies. Lastly, parathyroidectomy can be accomplished with >95% success rates with minimal morbidity, even in elderly patients and is the only curative treatment option for PHPT. Previous investigations have also documented that parathyroidectomy is more cost-effective than medical management or follow-up.
- u/s- Normal parathyroid glands are typically not visible due to their small size and similar acoustic character compared to thyroid tissue. They typically measure 2–4 mm in size and weigh 20–40 mg. Enlarged parathyroid glands are usually homogeneous, solid, hypoechoic masses that are less echogenic than thyroid tissue. They are typically between 8 and 15 mm in size and oval in shape, but they may become irregular when enlarged. Rarely, parathyroid adenomas are hyperechoic due to increased fat content. sestamibi scanning was more sensitive for larger adenomas; 93% of parathyroid adenomas that were >500 mg were seen, but only 51% of adenomas weighing <500 mg were identified. (MRI) has been associated in the published literature with a wide range of sensitivities for detecting abnormal parathyroid glands, from 43–82%.53,54 Abnormal parathyroid glands are usually hypointense on T1 images and hyper-intense on T2 images. However, the imaging characteristics vary based on the histology of the pathologic parathyroid gland, leading to an atypical appearance for 50% of parathyroid adenomas.55 Cervical lymph nodes have similar imaging characteristics and can be confused with abnormal parathyroid glands, which leads to false-positive results and muted enthusiasm for MRI as a preoperative localization study.
- Catheter-based localization with arteriography and venous sampling is reserved for remedial cases due to costs and risks of the procedures, including stroke, bleeding, hematoma, and contrast-induced nephropathy.
- A single adenoma is presumed to be the cause of a patient’s PHPT if only one parathyroid tumor is identified and the other parathyroid glands are normal, a situation present in about 80% of patients with PHPT The adenoma is dissected free of surrounding tissue (taking care not to fracture it), and the vascular pedicle is clamped, divided, and ligated Multiple adenomas (double or tirple) are more common in older patients with an incidence of up to 10% in patients >60 years old The abnormal glands should be excised, provided the remaining glands are confirmed as such, thus excluding asymmetric hyperplasia after biopsy and frozen section If all parathyroid glands are enlarged or hypercellular, patients have parathyroid hyperplasia that has been shown to occur in about 15% of patients in various series Patients may be treated by subtotal parathyroidectomy or by total parathyroidectomy and autotransplantation Sudies demonstrated equivalent cure rates and postoperative hypocalcemia for the two techniques Autotransplanted tissue may fail to function in about 5% of cases
- Patients who have undergone parathyroidectomy are advised to undergo calcium level checks 2 weeks postoperatively, at 6 months, and then annually. Recurrences are rare (<1%), except in patients with familial HPT. Recurrence rates of 15% at 2 years and 67% at 8 years have been reported for MEN1 patients.
- Recurrent disease is far less common than persistent HPT; however, both occur more frequently in the setting of familial HPT and MEN1, in particular. The most common causes for both these states include ectopic parathyroids, unrecognized hyperplasia, or supernumerary glands. More rare causes include parathyroid carcinoma, missed adenoma in a normal position, incomplete resection of an abnormal gland, parathyromatosis, or an inexperienced surgeon.
- Generally, these patients are approached with a focused exploration. The lateral approach is frequently used and can be achieved via the previous incision. The plane between the sternocleidomastoid and strap muscle is opened and allows for early identification of the RLN. Parathyroid tissue is cryopreserved routinely. Use of adjuncts, such as measuring intraoperative PTH levels, is critical to ensure adequate resection and avoid potentially harmful additional explorations. In case of difficult reexplorations, additional techniques such as bilateral internal jugular vein sampling for PTH, thyroid lobectomy on the side of the missing gland, cervical thymectomy, and ligation of the ipsilateral inferior thyroid artery (after lobectomy, to cause infarction of the missing gland) may be needed. Blind mediastinal exploration is not recommended. In patients who are denied, refuse, or fail exploration, medical options such as cinacalcet may be considered.
- Parathyroid cancer accounts for approximately 1% of PHPT cases. It may be suspected preoperatively by the presence of severe symptoms, serum calcium levels >14 mg/dL, significantly elevated PTH levels (five times normal), and a palpable parathyroid gland. Local invasion is quite common; approximately 15% of patients have lymph node metastases, and 33% have distant metastases at presentation. Intraoperatively, parathyroid cancer is suggested by the presence of a large, gray-white to gray-brown parathyroid tumor that is adherent to or invasive into surrounding tissues like muscle, thyroid, RLN, trachea, or esophagus. Enlarged lymph nodes also may be present. Frozen sections are generally unreliable. Accurate diagnosis necessitates histologic examination. The major diagnostic criteria include vascular or capsular invasion, trabecular or fibrous stroma, and frequent mitoses. It is, however, important to emphasize that these classic findings are not as frequently noted as previously reported, and some may be found in benign adenomas as well.
- Treatment of parathyroid cancer consists of neck exploration, with en bloc excision of the tumor and the ipsilateral thyroid lobe, in addition to the removal of contiguous lymph nodes (tracheoesophageal, paratracheal, and upper mediastinal). The recurrent nerve is not sacrificed unless it is directly involved with tumor. Adherent soft tissue structures (strap muscles or other soft tissues) should also be resected.89 Modified radical neck dissection is recommended in the presence of lateral lymph node metastases. Prophylactic neck dissection is not advised
- Reoperation is indicated for locally recurrent or metastatic disease to control hypercalcemia. Adjuvant radiation therapy should be considered in patients at high risk of local recurrence such as those with close or positive margins, invasion of surrounding structures, or tumor rupture. Radiation may also be used as primary therapy in unresectable disease or for palliation of bone metastases. Chemotherapy is not very effective. Bisphosphonates have shown some effectiveness in treating hypercalcemia associated with parathyroid carcinoma. Cinacalcet hydrochloride, a calcimimetic, can reduce PTH levels by directly binding to the CASR cells on the parathyroid gland and has been shown to be useful in controlling hypercalcemia in patients with refractory parathyroid carcinoma. Other promising approaches include antiparathyroid hormoneimmunotherapy, octreotide, and the telomerase inhibitor azidothymidine,