Parathyroid carcinoma - Clinicals, Diagnosis, and Management

Endocrine

Clinicals - History

Fact Explanation
Introduction Parathyroid carcinoma is a rare entity of endocrine malignancies thatcan cause heperparathyroidism.
Its course is typically indolent but progressive. It may be locally invasive or metastatic. This has a high mortality due to intractable hypercalcaemia.
Introduction
Parathyroid carcinoma is a rare entity of endocrine malignancies thatcan cause heperparathyroidism.
Its course is typically indolent but progressive. It may be locally invasive or metastatic. This has a high mortality due to intractable hypercalcaemia.
Asymptomatic Majority of neoplasms are secreting parathyroid hormone and appears as hyperparathyroidism. Only a small fraction is non-functional tumours. Asymptomatic
Majority of neoplasms are secreting parathyroid hormone and appears as hyperparathyroidism. Only a small fraction is non-functional tumours.
Hoarseness of voice Locally advanced disease causes infiltration of recurrent laryngeal nerve. Hoarseness of voice
Locally advanced disease causes infiltration of recurrent laryngeal nerve.
Dysphagia Locally advanced disease causes compressive symptoms. Dysphagia
Locally advanced disease causes compressive symptoms.
History of neck irradiation or exposure to radiation Exposure to radiation increases the risk of benign parathyroid diseases. Also it increases the risk of thyroid and parathyroid cancers. But evidences suggesting it as an etiologic factor in parathyroid carcinoma remains unclear. History of neck irradiation or exposure to radiation
Exposure to radiation increases the risk of benign parathyroid diseases. Also it increases the risk of thyroid and parathyroid cancers. But evidences suggesting it as an etiologic factor in parathyroid carcinoma remains unclear.
Family history of parathyroid carcinoma or hypeparathyroidism Parathyroid malignancies sometimes associated with hereditary syndromes of hyperparathyroidism, particularly in hyperparathyroidism-jaw tumor syndrome It is also associated with MEN-1 syndrome. Family history of parathyroid carcinoma or hypeparathyroidism
Parathyroid malignancies sometimes associated with hereditary syndromes of hyperparathyroidism, particularly in hyperparathyroidism-jaw tumor syndrome It is also associated with MEN-1 syndrome.
Recuurent epigastric pain radiating to back Associated with recurrent pancreatitis due to hypercalcaemia. Recuurent epigastric pain radiating to back
Associated with recurrent pancreatitis due to hypercalcaemia.
Symptoms of hypercalcaemia: :Fatigue, weakness, confusion, depression, constipation, polyuria, polydypsia The typical clinical picture is characterized by signs and symptoms of severe hypercalcemia. Symptoms of hypercalcaemia: :Fatigue, weakness, confusion, depression, constipation, polyuria, polydypsia
The typical clinical picture is characterized by signs and symptoms of severe hypercalcemia.
Bone pain and pathologic fractures Bones are frequently affected as parathyroid hormone causes bone resorption, leading to bone pain and pathological fractures and osteoporosis. Bone involvement due to hyperparathyroidism causes bone pain ,pathological fractures and other bone diseases. Bone pain and pathologic fractures
Bones are frequently affected as parathyroid hormone causes bone resorption, leading to bone pain and pathological fractures and osteoporosis. Bone involvement due to hyperparathyroidism causes bone pain ,pathological fractures and other bone diseases.
Renal colics Hypersecreted parathyroid hormone acts on kidney, and reduce the excretion of calcium via urine. Increased calcium can precipitate as stones This nephrocalcinosis causing loin to groin pain. Most of them are calcium oxalate and occasionally calcium phosphate. Renal colics
Hypersecreted parathyroid hormone acts on kidney, and reduce the excretion of calcium via urine. Increased calcium can precipitate as stones This nephrocalcinosis causing loin to groin pain. Most of them are calcium oxalate and occasionally calcium phosphate.
Neurological problems Neurological problems are a well defined manifestation of hyperparathyroidism. There can be abnormalities in calcium transport across the cell membrane due to hypercalcaemia. . Manifestations will be proximal muscle weakness, easy fatigubility, ansomnia, depression and poor memory. Neurological problems
Neurological problems are a well defined manifestation of hyperparathyroidism. There can be abnormalities in calcium transport across the cell membrane due to hypercalcaemia. . Manifestations will be proximal muscle weakness, easy fatigubility, ansomnia, depression and poor memory.

Clinicals - Examination

Fact Explanation
Palpable neck mass Most non-functional parathyroid carcinoma present as locally advanced disease. Palpable neck mass
Most non-functional parathyroid carcinoma present as locally advanced disease.
Hoarseness of voice Locally advanced disease causes infiltration of recurrent laryngeal nerve. Hoarseness of voice
Locally advanced disease causes infiltration of recurrent laryngeal nerve.
Keratopathy Calcium precipitation across the cornea in the palpebral aperture due to hypercalcaemia may cause keratopathy. Keratopathy
Calcium precipitation across the cornea in the palpebral aperture due to hypercalcaemia may cause keratopathy.
Pallor Aneamia may be due to several causes such as peptic ulcer disease due to hypercalcaemia, and hypercalcaemic nephropathy. Pallor
Aneamia may be due to several causes such as peptic ulcer disease due to hypercalcaemia, and hypercalcaemic nephropathy.
Dehydration Due to hypercalcaemia they can have polyuria, polydypsia. Dehydration
Due to hypercalcaemia they can have polyuria, polydypsia.
Depressed mood One of the major manifestation of hypercalcaemia. Depressed mood
One of the major manifestation of hypercalcaemia.
Nervous system examination: confusion, hypotonia,hyporeflexia, paresis, coma Due to the neurological manifestations in hypercalcaemia. Nervous system examination: confusion, hypotonia,hyporeflexia, paresis, coma
Due to the neurological manifestations in hypercalcaemia.
CVS Examination: low blood pressure and increase pulse rate/ irregular pulse Due to volume depletion and renal failure. CVS Examination: low blood pressure and increase pulse rate/ irregular pulse
Due to volume depletion and renal failure.
Abdominal examination: Fecal impaction , enlarged liver, epigastric tenderness Hypercalcaemia causes constipation, pancreatitis.This may also be due to due to metastasis there may be hepatic involvement. Abdominal examination: Fecal impaction , enlarged liver, epigastric tenderness
Hypercalcaemia causes constipation, pancreatitis.This may also be due to due to metastasis there may be hepatic involvement.

Investigations - Diagnosis

Fact Explanation
Serum Calcium Levels are usually elevated more markedly than seen with benign primary hyperparathyroidism. Parathyroid hormone assay is the most useful test for differentiating hyperparathyroidism from malignancy and other causes of hypercalcemia. Serum Calcium
Levels are usually elevated more markedly than seen with benign primary hyperparathyroidism. Parathyroid hormone assay is the most useful test for differentiating hyperparathyroidism from malignancy and other causes of hypercalcemia.
Serum calcium and phosphate level Calcium is almost always high. Serum phosphate may be low. Serum calcium and phosphate level
Calcium is almost always high. Serum phosphate may be low.
Alkaline phosphate level May be high due to bone resorption. Alkaline phosphate level
May be high due to bone resorption.
24 hour urinary calcium Increased due to hypercalcaemia. 24 hour urinary calcium
Increased due to hypercalcaemia.
X-ray -Hand -Skull Hand x-ray will show subperiosteal bone resorption of the distal phalanges. On X-ray imaging, brown tumors will be appearing as lytic lesions. Other changes would be osteopenia, 'salt-and-pepper' appearance on skull x-ray, subperiostal bone resorption and patchy diffuse areas of osteoclerosis. X-ray -Hand -Skull
Hand x-ray will show subperiosteal bone resorption of the distal phalanges. On X-ray imaging, brown tumors will be appearing as lytic lesions. Other changes would be osteopenia, 'salt-and-pepper' appearance on skull x-ray, subperiostal bone resorption and patchy diffuse areas of osteoclerosis.
Cervical ultrasound, computer tomography , CT scan and magnetic resonance imaging of the neck This will demonstrate the parathyroid adenoma, carcinoma and lymph node enlargement. Extent of the lesion, echogenic structure, solid areas may be seen. A CT scan of the neck and upper mediastinum may reveal a cystic tumor in the region. Advantages of USS are low costs, repeatability and no radiation load. Cervical ultrasound, computer tomography , CT scan and magnetic resonance imaging of the neck
This will demonstrate the parathyroid adenoma, carcinoma and lymph node enlargement. Extent of the lesion, echogenic structure, solid areas may be seen. A CT scan of the neck and upper mediastinum may reveal a cystic tumor in the region. Advantages of USS are low costs, repeatability and no radiation load.
Technetium-99m sestamibi (99mTc-MIBI) scintigraphy Technetium-99m sestamibi (99mTc-MIBI) scintigraphyis a basic important for the to the preoperative diagnosis. Technetium-99m sestamibi (99mTc-MIBI) scintigraphy
Technetium-99m sestamibi (99mTc-MIBI) scintigraphyis a basic important for the to the preoperative diagnosis.
FNAC and biopsy This may be harmful and care should be taken not tu rupture the capsule preoperetively. FNAC and biopsy
This may be harmful and care should be taken not tu rupture the capsule preoperetively.

Investigations - Management

Fact Explanation
Serum calcium levels Serum calcium levels needs to be monitored after surgery as there can be complications like hungry bone syndrome following parathyroidectomy. Calcium level returns to normal within 24 to 48 hours of surgery. Serum calcium levels
Serum calcium levels needs to be monitored after surgery as there can be complications like hungry bone syndrome following parathyroidectomy. Calcium level returns to normal within 24 to 48 hours of surgery.
Disease activity Serum calcium, phosphate and parathyroid hormone levels are important to assess disease activity. Disease activity
Serum calcium, phosphate and parathyroid hormone levels are important to assess disease activity.
DEXA scan Useful in patients who are known to have osteoporosis as a complication. DEXA scan
Useful in patients who are known to have osteoporosis as a complication.
Arterial blood gas Hyperchloremic metabolic acidosis occur in hyperparathyroidism. Arterial blood gas
Hyperchloremic metabolic acidosis occur in hyperparathyroidism.
Renal function tests(blood urea, serum creatinine, serum electrolytes) Loss of renal function is a can be a complication of hypercalcaemia, and phosphate retention. Renal function tests(blood urea, serum creatinine, serum electrolytes)
Loss of renal function is a can be a complication of hypercalcaemia, and phosphate retention.
Electrocardiogram Hypercalcaemia can cause shortening of QT interval and elevation of ST segment which can mimics acute myocardial infarction. Electrocardiogram
Hypercalcaemia can cause shortening of QT interval and elevation of ST segment which can mimics acute myocardial infarction.
Echocardiogram There can be left ventricular hypertrophy and myocardial calcific deposits. Echocardiogram
There can be left ventricular hypertrophy and myocardial calcific deposits.
DEXA scan (Dual-emission X-ray absorptiometry) This is to detect osteoporosis and Z -score <-2.0 forearm is suggestive of osteoporosis. DEXA scan (Dual-emission X-ray absorptiometry)
This is to detect osteoporosis and Z -score <-2.0 forearm is suggestive of osteoporosis.

Management - Supportive

Fact Explanation
Patient education Patient should be educated on the nature of the disease, complication, treatment options and side effects of the treatments. Its course is typically indolent but may be progressive. Proper counselling about the complications of the surgery is required. Patient education
Patient should be educated on the nature of the disease, complication, treatment options and side effects of the treatments. Its course is typically indolent but may be progressive. Proper counselling about the complications of the surgery is required.
Resuscitaion ABCDE checcck up to assess the airway, breathing, circulation, disability, and examination and evaluation is nesessary in emergency situations as acute management of hypercalcaemia. Resuscitaion
ABCDE checcck up to assess the airway, breathing, circulation, disability, and examination and evaluation is nesessary in emergency situations as acute management of hypercalcaemia.
Rehydration Hypercalcemia caused by parathyroid cancer is often severe. Rehydration would be one of the earliest step in managing hypercalcaemia. Aggressive rehydration with intravenous (IV) normal saline is required. Rehydration
Hypercalcemia caused by parathyroid cancer is often severe. Rehydration would be one of the earliest step in managing hypercalcaemia. Aggressive rehydration with intravenous (IV) normal saline is required.
Management of hypercalcaemia Phosphate therapy can be used to correct hypercalcaemia as an oral or parentaral therapy. This would be the choice in managing patients with hypercalcaemia after failed parathyroidectomy. 1-3g of phosphorous per day is given with checking Ca daily in the initial period. Acute hypercalcaemia can be managed with intravenous phosphate therapy specially if the patient is in coma situation. This improves the calcium soon, but patient should be started on oral phosphate as soon as possible. Sodium ethylene diamine tetraacetate is a calcium chelating agent. Given as an intravenous infusion. Furosemide Helps in excretion of calcium. It is contraindicated in kidney failure. Calcitonin is important in managing severe hypercalcaemia by inhibiting the bone turn over. Management of hypercalcaemia
Phosphate therapy can be used to correct hypercalcaemia as an oral or parentaral therapy. This would be the choice in managing patients with hypercalcaemia after failed parathyroidectomy. 1-3g of phosphorous per day is given with checking Ca daily in the initial period. Acute hypercalcaemia can be managed with intravenous phosphate therapy specially if the patient is in coma situation. This improves the calcium soon, but patient should be started on oral phosphate as soon as possible. Sodium ethylene diamine tetraacetate is a calcium chelating agent. Given as an intravenous infusion. Furosemide Helps in excretion of calcium. It is contraindicated in kidney failure. Calcitonin is important in managing severe hypercalcaemia by inhibiting the bone turn over.

Management - Specific

Fact Explanation
Surgery Parathyroid carcinoma can often be cured by adequate surgical excision at an early stage. Meticulous en bloc resection is the onlyoption available for the cure of parathyroid cancer. Rupture of the tumor capsule either preoperatively during needle aspiration or intraoperatively should be happened. Aggressive en bloc removal of the affected parathyroid gland with ipsilateral thyroidectomy and isthmusectomy should bedone and the sample is sent for histopathological analysisto see the local vascular, capsular, and soft tissue invasion of the tumour. Surgery
Parathyroid carcinoma can often be cured by adequate surgical excision at an early stage. Meticulous en bloc resection is the onlyoption available for the cure of parathyroid cancer. Rupture of the tumor capsule either preoperatively during needle aspiration or intraoperatively should be happened. Aggressive en bloc removal of the affected parathyroid gland with ipsilateral thyroidectomy and isthmusectomy should bedone and the sample is sent for histopathological analysisto see the local vascular, capsular, and soft tissue invasion of the tumour.
Post op care Hungry bone syndrome is a significant complication occurring after surgical removal of parathyroids and may require postoperative calcium. It is a postoperative hypocalcemic state as a result of remineralization of various minerals, including calcium, of the bone. It needs long-term supplementation of calcium. Post op care
Hungry bone syndrome is a significant complication occurring after surgical removal of parathyroids and may require postoperative calcium. It is a postoperative hypocalcemic state as a result of remineralization of various minerals, including calcium, of the bone. It needs long-term supplementation of calcium.
Management of metastases Distant metastases are less frequent in parathyroid carcinoma and is causing , hypercalcemia that is poorly controlled by hormonal, chemotherapy, or radiation therapy. Management of metastases
Distant metastases are less frequent in parathyroid carcinoma and is causing , hypercalcemia that is poorly controlled by hormonal, chemotherapy, or radiation therapy.
Management of recurrances Carcinoma already spread outside the capsule or implanted at surgery, increases the chance of local recurrence. Reoperation for local and regional recurrence is the option for management. Management of recurrances
Carcinoma already spread outside the capsule or implanted at surgery, increases the chance of local recurrence. Reoperation for local and regional recurrence is the option for management.
External beam radiation therapy External beam radiation therapy (EBRT) is controversial, but may be given to the carcinoma with capsular invasion on histopathology as an adjuvant therapy. It is administered to the tumor bed and regional lymphatics. External beam radiation therapy
External beam radiation therapy (EBRT) is controversial, but may be given to the carcinoma with capsular invasion on histopathology as an adjuvant therapy. It is administered to the tumor bed and regional lymphatics.
Chemotherapy Synthetic oestrogen compounds are useful in treatin g the metastatic carcinoma. Chemotherapy
Synthetic oestrogen compounds are useful in treatin g the metastatic carcinoma.

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