Hyperparathyroidism

Endocrinology, Metabolism and Nutrition

Clinicals - History

Fact Explanation
Malaise, fatigue, weakness, myalgia Hyperparathyroidsm is mostly seen in post menopausal women and they mostly present with these vague symptoms.
Parathyroid increases calcium levels by increasing its release from bone, increasing absorption from intestine and reabsorption in renal tubules.
Malaise, fatigue, weakness, myalgia
Hyperparathyroidsm is mostly seen in post menopausal women and they mostly present with these vague symptoms.
Parathyroid increases calcium levels by increasing its release from bone, increasing absorption from intestine and reabsorption in renal tubules.
Depression, mood disturbances, dementia, confusion, and stupor Whether neuropsychological complaints may improve with surgery or not, is not consistent, thus it is not considered as an indication for surgery. Depression, mood disturbances, dementia, confusion, and stupor
Whether neuropsychological complaints may improve with surgery or not, is not consistent, thus it is not considered as an indication for surgery.
Constipation Occurs due to hypercalcaemia. Constipation
Occurs due to hypercalcaemia.
Loin pain, dysuria, haematuria Formation of renal stones occurs due to hypercalcaemia, this may later lead to urinary tract infection and patient may present with its symptoms.
This may also lead to renal impairment and hypertension, symptoms of which may also be patient's presentation.
Loin pain, dysuria, haematuria
Formation of renal stones occurs due to hypercalcaemia, this may later lead to urinary tract infection and patient may present with its symptoms.
This may also lead to renal impairment and hypertension, symptoms of which may also be patient's presentation.
Polyuria, polydipsia and dehydration Nephrogenic diabetes insipidus is caused by hypercalcaemia. Polyuria, polydipsia and dehydration
Nephrogenic diabetes insipidus is caused by hypercalcaemia.
Fracture after trivial injury Pathological fractures may occur in hyperparathyroidism. Fracture after trivial injury
Pathological fractures may occur in hyperparathyroidism.
Bone pain, deformity, bony lumps Due to osteoporosis, fractures and bone tumors. Bone pain, deformity, bony lumps
Due to osteoporosis, fractures and bone tumors.
Features of chronic kidney disease: anorexia, nausea, dry skin, pruritus, restless leg, reduced urine output Chronic kidney disease results in reduced formation of active vitamin D which subsequently results in reduced calcium level which is a stimulant to parathyroid glands resulting in secondary hyperparathyroidism.
Nephrocalcinosis and renal stone formation seen in hyperparathyroidism itself can lead to renal impairment.
Features of chronic kidney disease: anorexia, nausea, dry skin, pruritus, restless leg, reduced urine output
Chronic kidney disease results in reduced formation of active vitamin D which subsequently results in reduced calcium level which is a stimulant to parathyroid glands resulting in secondary hyperparathyroidism.
Nephrocalcinosis and renal stone formation seen in hyperparathyroidism itself can lead to renal impairment.
Recurrent acute pancreatitis : Acute severe abdominal pain, radiating to the back, relieved by bending forwards. Hypercalcemia, may activate trypsinogen to trypsin leading to auto digestion of pancreas causing pancreatitis or may lead to formation of pancreatic calculi obstructing the duct leading to acute or chronic pancreatitis Recurrent acute pancreatitis : Acute severe abdominal pain, radiating to the back, relieved by bending forwards.
Hypercalcemia, may activate trypsinogen to trypsin leading to auto digestion of pancreas causing pancreatitis or may lead to formation of pancreatic calculi obstructing the duct leading to acute or chronic pancreatitis
Family history Multiple endocrine neoplasia syndromes (MEN-1, MEN-2) is associated with hyperparathyroidism. Family history
Multiple endocrine neoplasia syndromes (MEN-1, MEN-2) is associated with hyperparathyroidism.
Exposure to radiation: external-beam radiotherapy Irradiation for acne Irradiation for acne has 2-3 fold increase in this disease. MEN-1 gene mutation is also associated with irradiation. Exposure to radiation: external-beam radiotherapy Irradiation for acne
Irradiation for acne has 2-3 fold increase in this disease. MEN-1 gene mutation is also associated with irradiation.
Drug history: Lithium, anticonvulsants Prolonged use of lithium (as used in psychiatric diseases) or anticonvulsant is associated with primary hyperparathyroidism. Drug history: Lithium, anticonvulsants
Prolonged use of lithium (as used in psychiatric diseases) or anticonvulsant is associated with primary hyperparathyroidism.
Diet history: milk allergy/ lactose intolerence, intake of ample phytates along with meal Reduced calcium intake or absorption will lead to hypocalcaemia and secondary hyperparathyroidism. Diet history: milk allergy/ lactose intolerence, intake of ample phytates along with meal
Reduced calcium intake or absorption will lead to hypocalcaemia and secondary hyperparathyroidism.
Exposure to sun light Reduced exposure may result in vitamin D deficiency leading to hypocalcaemia and subsequent secondary hyperparathyroidism. Exposure to sun light
Reduced exposure may result in vitamin D deficiency leading to hypocalcaemia and subsequent secondary hyperparathyroidism.
Lactation/ growth These states are associated with high demand to vitamin D and calcium and lack of it leads to secondary hyperparathyroidism. Lactation/ growth
These states are associated with high demand to vitamin D and calcium and lack of it leads to secondary hyperparathyroidism.

Clinicals - Examination

Fact Explanation
Bony "tumors", mostly seen at facial bones, clavicle, ribs, pelvis, and/or femur Due to brown tumors which arise at the terminal stages of bone remodelling that occurs in hyperparathyroidism. Bony "tumors", mostly seen at facial bones, clavicle, ribs, pelvis, and/or femur
Due to brown tumors which arise at the terminal stages of bone remodelling that occurs in hyperparathyroidism.
Signs of dehydration: presence of tear, enophthalmos, skin turgor, capillary refilling time Hyperthyroidism is associated with nephrogenic diabetes insipidus leading to dehydration. It should be addressed immediately if present. Signs of dehydration: presence of tear, enophthalmos, skin turgor, capillary refilling time
Hyperthyroidism is associated with nephrogenic diabetes insipidus leading to dehydration. It should be addressed immediately if present.
Blood pressure Hypertension is associated with hyperparathyroidism. Blood pressure
Hypertension is associated with hyperparathyroidism.
Features of chronic failure may present: dry skin, scratch marks, oedema, basal crepitations in lung This may have lead to secondary hyperparathyroidism. Features of chronic failure may present: dry skin, scratch marks, oedema, basal crepitations in lung
This may have lead to secondary hyperparathyroidism.

Investigations - Diagnosis

Fact Explanation
Plasma albumin-adjusted calcium >2·65 mmol/L on two occasions Primary hyperparathyroidism is the most common
cause of hypercalcaemia
Plasma albumin-adjusted calcium >2·65 mmol/L on two occasions
Primary hyperparathyroidism is the most common
cause of hypercalcaemia
Parathyroid hormone Should be measured before it is altered by any medical intervention.
If >3·0 pmol/L it is caused by hyperparathyroidism, if <3·0 pmol/L non-parathyroid related causes may have caused the hypercalcaemia
Parathyroid hormone
Should be measured before it is altered by any medical intervention.
If >3·0 pmol/L it is caused by hyperparathyroidism, if <3·0 pmol/L non-parathyroid related causes may have caused the hypercalcaemia
Urine calcium creatinine clearance ratio To exclude familial benign hypocalciuric hypercalcaemia(FBHH), if <0·01 FBHH is more likely than hyperparathyroidism. Urine calcium creatinine clearance ratio
To exclude familial benign hypocalciuric hypercalcaemia(FBHH), if <0·01 FBHH is more likely than hyperparathyroidism.
X ray Depending on patients symptoms necessary images are obtained. Nephrocalcinosis, renal calculi, osteopenic changes, changes due to demineralization, Brown tumour, 'Salt and pepper' appearance in skull, fracture of femur, pathological fracture could be seen. X ray
Depending on patients symptoms necessary images are obtained. Nephrocalcinosis, renal calculi, osteopenic changes, changes due to demineralization, Brown tumour, 'Salt and pepper' appearance in skull, fracture of femur, pathological fracture could be seen.
2D echocardiography Cardiac and valvular calcification maybe present. Also hyperparathyroidism is associated with hypertension which in turn might cause left ventricular hypertrophy(LVH). LVH is also a powerful predictor of cardiovascular mortality which is the common cause of death in hyperparathyroidism. 2D echocardiography
Cardiac and valvular calcification maybe present. Also hyperparathyroidism is associated with hypertension which in turn might cause left ventricular hypertrophy(LVH). LVH is also a powerful predictor of cardiovascular mortality which is the common cause of death in hyperparathyroidism.
CT abdomen Renal stones and calcification, changes of acute pancretitis if presented with it can be seen. CT abdomen
Renal stones and calcification, changes of acute pancretitis if presented with it can be seen.
Ultrasonography neck Enlarged parathyroid gland is visualised as hypoechoic lesion Ultrasonography neck
Enlarged parathyroid gland is visualised as hypoechoic lesion
CT/ Magnetic resonance of the gland They are used to locate the pathological gland pre operatively. Magnetic resonance with gadolinium and fat suppression helps to visualise the anatomy of neck clearly. CT/ Magnetic resonance of the gland
They are used to locate the pathological gland pre operatively. Magnetic resonance with gadolinium and fat suppression helps to visualise the anatomy of neck clearly.
Parathyroid scintigraphy 99'Tc-Sestamibi is the agent of choice, since its not uptaken by thyroid gland and the abnormal parathyroid gland is clearly visualised. Parathyroid scintigraphy
99'Tc-Sestamibi is the agent of choice, since its not uptaken by thyroid gland and the abnormal parathyroid gland is clearly visualised.
Positron emission tomography/computed tomography (PET/CT) Disease extend and response to treatment is well demonstrated in parathyroid cancer by PET CT. Positron emission tomography/computed tomography (PET/CT)
Disease extend and response to treatment is well demonstrated in parathyroid cancer by PET CT.

Investigations - Management

Fact Explanation
Serum calcium and creatinine annually and dual-energy x-ray absorptiometry (DEXA) annually or 2 yearly according to clilnical judegment. These tests are done on patient who do not undergo surgery but are under medical management only. Serum calcium and creatinine annually and dual-energy x-ray absorptiometry (DEXA) annually or 2 yearly according to clilnical judegment.
These tests are done on patient who do not undergo surgery but are under medical management only.
Post operative serum calcium 4 hourly for 2 days and then daily for 7-14 days till the levels are stable, and parathyroid hormone levels. Most patients may develop hypocalcaemia which could be easily treated with calcium supplements but only few will need long term calcium supplements.
Persistently elevated parathyroid hormone level needs to be addressed and sometime re-exploration maybe needed.
Post operative serum calcium 4 hourly for 2 days and then daily for 7-14 days till the levels are stable, and parathyroid hormone levels.
Most patients may develop hypocalcaemia which could be easily treated with calcium supplements but only few will need long term calcium supplements.
Persistently elevated parathyroid hormone level needs to be addressed and sometime re-exploration maybe needed.
Basic investigations for surgery: Chest x-ray, ECG, full blood count, haemostasis, renal function, random glucose Should be tailor made according to ASA (American Society of Anesthesiologists) grade the individual patient would fall in. Basic investigations for surgery: Chest x-ray, ECG, full blood count, haemostasis, renal function, random glucose
Should be tailor made according to ASA (American Society of Anesthesiologists) grade the individual patient would fall in.
DNA sequence testing Used to screen patients with asymptomatic hyperparathyroidism or hypercalcemia DNA sequence testing
Used to screen patients with asymptomatic hyperparathyroidism or hypercalcemia
Serum 25-hydroxyvitamin D levels In patients with asymptomatic primary hyperparathyroidism there could be associated vitamin D insufficiency which should be treated if present. Serum 25-hydroxyvitamin D levels
In patients with asymptomatic primary hyperparathyroidism there could be associated vitamin D insufficiency which should be treated if present.
Estimated glomerular filtration rate (GFR) This determines the renal function and if GFR is less than 60 ml/min.1.73 m² in established asymptomatic primary hyperparathyroidism surgery should be considered. Estimated glomerular filtration rate (GFR)
This determines the renal function and if GFR is less than 60 ml/min.1.73 m² in established asymptomatic primary hyperparathyroidism surgery should be considered.
Regular serum calcium and three-site bone mineral density (BMD) Should be done in follow up of those who have not undergone surgery for asymptomatic primary hyperparathyroidism because some patients develop decreased BMD after 8-10 years. Regular serum calcium and three-site bone mineral density (BMD)
Should be done in follow up of those who have not undergone surgery for asymptomatic primary hyperparathyroidism because some patients develop decreased BMD after 8-10 years.

Management - Supportive

Fact Explanation
Rehydration with NaCl. Patients are usually dehydrated and rehydration with NaCl will replenish the lost volume, decrease uraemia and improve calcium excretion in urine. Rehydration with NaCl.
Patients are usually dehydrated and rehydration with NaCl will replenish the lost volume, decrease uraemia and improve calcium excretion in urine.

Management - Specific

Fact Explanation
Medical management Bisphosphonates, hormone replacement therapy, raloxifene and calcimimetics (cinacalcet) Reduces the serum calcium and parathyroid hormone levels.
Consider in patient with no indication or contraindications to surgery.
Calcimimetics, mimic calcium on parathyroid receptors and reduces its response to hypocalcaemia.
Medical management
Bisphosphonates, hormone replacement therapy, raloxifene and calcimimetics (cinacalcet) Reduces the serum calcium and parathyroid hormone levels.
Consider in patient with no indication or contraindications to surgery.
Calcimimetics, mimic calcium on parathyroid receptors and reduces its response to hypocalcaemia.
Surgical management Serum albumin-adjusted calcium > 0·25 mmol/L above the upper limit of local laboratory reference range, urine calcium > 10 mmol/24 hours, in creatinine clearance ≥ 30%, bone mineral density T score < –2·5, age < 50 years, on patient's request/ when adequate follow-up is unlikely. Even in asymptomatic primary hyperparathyroidism surgery is considered if renal impairment is present or bone density T-score of lumbar spine, hip, or distal one third radius is -2.5 or less. Minimally invasive parathyroidectomy has low morbidity and high patient satisfaction Adenoma is removed or in cases of hyperplasia of all 4 glands, 3 1/2 of the gland is removed.
Total or subtotal parathyroidectomy is performed in tertiary hyperparathyroidism
Surgery leads to long-term improvement in bone mineral density of spine, hip, and radius in asymptomatic primary hyperparathyroidism .
Surgical management
Serum albumin-adjusted calcium > 0·25 mmol/L above the upper limit of local laboratory reference range, urine calcium > 10 mmol/24 hours, in creatinine clearance ≥ 30%, bone mineral density T score < –2·5, age < 50 years, on patient's request/ when adequate follow-up is unlikely. Even in asymptomatic primary hyperparathyroidism surgery is considered if renal impairment is present or bone density T-score of lumbar spine, hip, or distal one third radius is -2.5 or less. Minimally invasive parathyroidectomy has low morbidity and high patient satisfaction Adenoma is removed or in cases of hyperplasia of all 4 glands, 3 1/2 of the gland is removed.
Total or subtotal parathyroidectomy is performed in tertiary hyperparathyroidism
Surgery leads to long-term improvement in bone mineral density of spine, hip, and radius in asymptomatic primary hyperparathyroidism .

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