Secondary hyperparathyroidism - Clinicals, Diagnosis, and Management

Endocrinology, Metabolism and Nutrition

Clinicals - History

Fact Explanation
History of chronic kidney disease (CKD) Stimuli for the development of secondary hyperparathyroidism would be elevated extracellular phosphate concentration, decreased ionized calcium concentration, and reduced serum calcitriol. Phosphate retention can occur in CKD patients together with impaired production of calcitriol. There can be resistance to the action of PTH in the bones. Decreased serum calcium is sensed by the parathyroid calcium receptors. These factors can lead to hypersecretion of the parathyroid hormone by the parathyroid glands. There are evidence about fibroblast growth factor: that elevated FGF aggravates the deficiency of calcitriol, thus exacerbating the hyperparathyroidism. When the parathyroid stimulation occurs for a long time there can be hyperplasia of the parathyroid gland. History of chronic kidney disease (CKD)
Stimuli for the development of secondary hyperparathyroidism would be elevated extracellular phosphate concentration, decreased ionized calcium concentration, and reduced serum calcitriol. Phosphate retention can occur in CKD patients together with impaired production of calcitriol. There can be resistance to the action of PTH in the bones. Decreased serum calcium is sensed by the parathyroid calcium receptors. These factors can lead to hypersecretion of the parathyroid hormone by the parathyroid glands. There are evidence about fibroblast growth factor: that elevated FGF aggravates the deficiency of calcitriol, thus exacerbating the hyperparathyroidism. When the parathyroid stimulation occurs for a long time there can be hyperplasia of the parathyroid gland.
Dietary vitamin D defeciency and rickets Vitamin D is important in absorption of calcium from the gastrointestinal tract, tubular reabsorption of calcium and resorption of bone. Rickets is mainly due to lack of vitamin D and calcium. When the vitamin D is lacking, low calcium triggers parathyroid glands to increase the secretion of parathyroid hormone causing secondary hyperparathyroidism. They may have following features: weak tooth enamel with delay in tooth eruption and increased risk of cavities, pathological fractures, bone pain and poor growth. Dietary vitamin D defeciency and rickets
Vitamin D is important in absorption of calcium from the gastrointestinal tract, tubular reabsorption of calcium and resorption of bone. Rickets is mainly due to lack of vitamin D and calcium. When the vitamin D is lacking, low calcium triggers parathyroid glands to increase the secretion of parathyroid hormone causing secondary hyperparathyroidism. They may have following features: weak tooth enamel with delay in tooth eruption and increased risk of cavities, pathological fractures, bone pain and poor growth.
Renal colic Hypersecreted parathyroid hormone acts on kidney, and reduce the excretion of calcium via urine. Increased calcium can precipitate as stones. This nephrocalcinosis causes loin to groin pain. Most of them are calcium oxalate and occasionally calcium phosphate. Renal colic
Hypersecreted parathyroid hormone acts on kidney, and reduce the excretion of calcium via urine. Increased calcium can precipitate as stones. This nephrocalcinosis causes loin to groin pain. Most of them are calcium oxalate and occasionally calcium phosphate.
Skeletal problems Renal osteodystrophy is the term used for the bone problems associated with chronic kidney disease. Parathyroid hormone causes bone resorption, leading to abnormal bone
mineralization, bone pain, pathological fractures and osteoporosis.
Skeletal problems
Renal osteodystrophy is the term used for the bone problems associated with chronic kidney disease. Parathyroid hormone causes bone resorption, leading to abnormal bone
mineralization, bone pain, pathological fractures and osteoporosis.
Skin pruritus This may be due to calcium depositions in the skin. Secondary hyperparathyroidism developing in a patient with underlying chronic kidney disease, may exacerbate the pre existing itching due to uremia. Skin pruritus
This may be due to calcium depositions in the skin. Secondary hyperparathyroidism developing in a patient with underlying chronic kidney disease, may exacerbate the pre existing itching due to uremia.
Constipation, polyuria and polydypsia Due to hypercalcaemia. Hypercalcaemia can occur in severe disease. Constipation, polyuria and polydypsia
Due to hypercalcaemia. Hypercalcaemia can occur in severe disease.
Myopathy and muscle weakness Neurological problems can be occasionally associated with hyperparathyroidism. Myopathy and muscle weakness
Neurological problems can be occasionally associated with hyperparathyroidism.
Fatigue, shortness of breath, ankle swelling, facial puffiness There can be associated chronic kidney disease giving rise to complications such as anaemia causing fatigue, shortness of breath etc, cardiovascular problems such as myocardial infarction, and peripheral oedema : ankle swelling, facial puffiness. Fatigue, shortness of breath, ankle swelling, facial puffiness
There can be associated chronic kidney disease giving rise to complications such as anaemia causing fatigue, shortness of breath etc, cardiovascular problems such as myocardial infarction, and peripheral oedema : ankle swelling, facial puffiness.

Clinicals - Examination

Fact Explanation
Pallor Is seen in chronic kidney disease. Osteitis fibrosa in renal osteodystrophy can aggravate the marrow fibrosis and worsen the anaemia. Pallor
Is seen in chronic kidney disease. Osteitis fibrosa in renal osteodystrophy can aggravate the marrow fibrosis and worsen the anaemia.
Skin pigmentation, peripheral oedema Due to underlying chronic kidney disease. Skin pigmentation, peripheral oedema
Due to underlying chronic kidney disease.
Features of rickets: Widening of wrist and ankle joint, bowing of the legs, rickety rossery, curvature of the spine, softening of skull bones. Rickets can presents with secondary hyperparathyroidism. Features of rickets: Widening of wrist and ankle joint, bowing of the legs, rickety rossery, curvature of the spine, softening of skull bones.
Rickets can presents with secondary hyperparathyroidism.
Arrhythmia , features of heart failure: elevated jugular venous pressure. hepatomegally, peripheral oedema, fine end inspiratory bibasal crepitations Development of vascular calcification is is a complication of secondary hyperparathyroidism, due to the elevated levels of calcium and phosphorous. Calcifications can affect the myocardium, the conduction system, and valves. Myocardial fibrosis can leads to left ventricular dysfunction. Arrhythmia , features of heart failure: elevated jugular venous pressure. hepatomegally, peripheral oedema, fine end inspiratory bibasal crepitations
Development of vascular calcification is is a complication of secondary hyperparathyroidism, due to the elevated levels of calcium and phosphorous. Calcifications can affect the myocardium, the conduction system, and valves. Myocardial fibrosis can leads to left ventricular dysfunction.
Scratch marks Pruritus due to secondary hyperparathyroidism and underlying chronic kidney disease. Scratch marks
Pruritus due to secondary hyperparathyroidism and underlying chronic kidney disease.

Investigations - Diagnosis

Fact Explanation
Serum parathyroid hormone level Elevated PTH secondary hyperparathyroidism due to CKD, occurs during the early disease and signals the need for an intervention. PTH level > 450 pg/dl is associated with advanced bone turnover. Serum parathyroid hormone level
Elevated PTH secondary hyperparathyroidism due to CKD, occurs during the early disease and signals the need for an intervention. PTH level > 450 pg/dl is associated with advanced bone turnover.
Serum calcium Low-normal calcium is seen. But severe may have elevated serum calcium. Serum calcium
Low-normal calcium is seen. But severe may have elevated serum calcium.
Serum phosphate High in real failure due to phosphate retention and low in vitamin D deficiency. Serum phosphate
High in real failure due to phosphate retention and low in vitamin D deficiency.
Alkaline phosphate level May be high due to bone resorption. Alkaline phosphate level
May be high due to bone resorption.
Vitamin D metabolite Serum 25-hydroxyvitamin D levels should be measured and correction should be done in a deficiency. Vitamin D metabolite
Serum 25-hydroxyvitamin D levels should be measured and correction should be done in a deficiency.
X-ray Bone resorption can be seen in several locations in the bones. Bone resorption, periosteal reaction, and brown tumors, osteoporosis, osteosclerosis, osteomalacia, and soft-tissue and vascular calcifications are the frequent pathological features seen in secondary hyperparathyroidism. 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 with trabecular resorption, subperiostal bone resorption and patchy diffuse areas of osteoclerosis. X-ray
Bone resorption can be seen in several locations in the bones. Bone resorption, periosteal reaction, and brown tumors, osteoporosis, osteosclerosis, osteomalacia, and soft-tissue and vascular calcifications are the frequent pathological features seen in secondary hyperparathyroidism. 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 with trabecular resorption, subperiostal bone resorption and patchy diffuse areas of osteoclerosis.

Investigations - Management

Fact Explanation
Serum PTH Targets of treatment: 35-70 pg/ml in stage 3, 70-110 pg/ml in stage 4 and 150-300 pg/ml in stage 5. Serum PTH
Targets of treatment: 35-70 pg/ml in stage 3, 70-110 pg/ml in stage 4 and 150-300 pg/ml in stage 5.
Serum calcium level This should be reduced to normal levels in stage 3 and 4, and 2.1-2.4 mmol/l in stage 5. Serum calcium level
This should be reduced to normal levels in stage 3 and 4, and 2.1-2.4 mmol/l in stage 5.
Serum phosphate level Targets for the management of hyperphosphataemia include 2.7 to 4.6 mg/dl in patients with CKD stage 3 to 4 and 3.5 to 5.5 mg/dl in CKD stage 5. Serum phosphate level
Targets for the management of hyperphosphataemia include 2.7 to 4.6 mg/dl in patients with CKD stage 3 to 4 and 3.5 to 5.5 mg/dl in CKD stage 5.
Arterial blood gas analysis Hyperchloremic metabolic acidosis occur in hyperparathyroidism. Arterial blood gas analysis
Hyperchloremic metabolic acidosis occur in hyperparathyroidism.
Screen for diabetes mellitus :HbA1c, fasting blood sugar CKD patients may have underlying diabetes mellitus that needs follow up. Screen for diabetes mellitus :HbA1c, fasting blood sugar
CKD patients may have underlying diabetes mellitus that needs follow up.
Electrocardiogarm Myocardial fibrosis secondary cardiac calcification can leads to left ventricular hypertrophy. Prominent R wave in V5 or V6 and prominent S wave in V1 or V2 is seen on ECG. Electrocardiogarm
Myocardial fibrosis secondary cardiac calcification can leads to left ventricular hypertrophy. Prominent R wave in V5 or V6 and prominent S wave in V1 or V2 is seen on ECG.
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 <-2.5 is associated with high risk of fractures. DEXA scan (Dual-emission X-ray absorptiometry)
This is to detect osteoporosis and Z -score <-2.5 is associated with high risk of fractures.
Renal function tests(blood urea, serum creatinine, serum electrolytes, glomerular filtration rate) CKD patients need regular assessment of renal functions. Renal function tests(blood urea, serum creatinine, serum electrolytes, glomerular filtration rate)
CKD patients need regular assessment of renal functions.

Management - Supportive

Fact Explanation
Dietary phosphate restriction Hyperphosphatemia is known to be associated with the increased risk of death in patients with end stage renal failure. Dietary phosphate restriction can be done if parathyroid hormone level is high. This is also important in preventing the development of hyperparathyroidism. Dietary phosphates are included in colas, nuts, peas, beans, and dairy product . Dietary phosphate restriction
Hyperphosphatemia is known to be associated with the increased risk of death in patients with end stage renal failure. Dietary phosphate restriction can be done if parathyroid hormone level is high. This is also important in preventing the development of hyperparathyroidism. Dietary phosphates are included in colas, nuts, peas, beans, and dairy product .
Management of complications due to secondary hyperparathyroidism Vascular complications, bone complications may need specific attention. For example heart failure may needs loop diuretics. Management of complications due to secondary hyperparathyroidism
Vascular complications, bone complications may need specific attention. For example heart failure may needs loop diuretics.
Prevention of falls As the patients are having osteoporosis , they are vulnerable to fractures, therefore measures should be taken to prevent falls and fractures. Prevention of falls
As the patients are having osteoporosis , they are vulnerable to fractures, therefore measures should be taken to prevent falls and fractures.
Management of chronic kidney disease and its complications Hypertension, dyslipidaemia, anaemia, diabetes mellitus, uremia and cardiovascular complications need appropriate management. Management of chronic kidney disease and its complications
Hypertension, dyslipidaemia, anaemia, diabetes mellitus, uremia and cardiovascular complications need appropriate management.
Prevention of secondary hyperparathyroidism Early diagnosis and treatment of rickets or vitamin D deficiency and proper management of chronic kidney disease is important in this aspect. Prevention of secondary hyperparathyroidism
Early diagnosis and treatment of rickets or vitamin D deficiency and proper management of chronic kidney disease is important in this aspect.

Management - Specific

Fact Explanation
Vitamin D supplementation Vitamin D supplementation as alfacalcidol, and newer vitamin D analogues such as doxercalciferol, 22-oxacalcitriol, or paricalcitol is done in chronic kidney disease patients. Vitamin D enhance the absorption of calcium and phosphorous from the gut , then reduce the synthesis of PTH. Vitamin D supplementation
Vitamin D supplementation as alfacalcidol, and newer vitamin D analogues such as doxercalciferol, 22-oxacalcitriol, or paricalcitol is done in chronic kidney disease patients. Vitamin D enhance the absorption of calcium and phosphorous from the gut , then reduce the synthesis of PTH.
Phosphate binders, and the more recent calcimimetics As there is associated hyperphosphataemia, phosphate binders are used to reduce phosphate level in the blood. Calcium-free phosphate binders, (sevelamer and lanthanum carbonate) are used instead of calcium salts, as calcium salts can bring down the phosphorous levels to normal while increasing the possibility of complications such as hypercalcemia, calciphylaxis, and vascular calcifications. Phosphate binders, and the more recent calcimimetics
As there is associated hyperphosphataemia, phosphate binders are used to reduce phosphate level in the blood. Calcium-free phosphate binders, (sevelamer and lanthanum carbonate) are used instead of calcium salts, as calcium salts can bring down the phosphorous levels to normal while increasing the possibility of complications such as hypercalcemia, calciphylaxis, and vascular calcifications.
Calcimimetics eg:- Cinacalcet This increases sensitivity of calcium receptors and reduce PTH secretion by the parathyroid glands. Calcimimetics also acts to reduce the vitamin D-induced vascular calcifications. Calcimimetics eg:- Cinacalcet
This increases sensitivity of calcium receptors and reduce PTH secretion by the parathyroid glands. Calcimimetics also acts to reduce the vitamin D-induced vascular calcifications.
Bisphosphonates Reduce the rate of bone resorption. Bisphosphonates
Reduce the rate of bone resorption.
Newer therapies Selective percutaneous ethanol injection therapy and direct injection with active vitamin D compounds such as calcitriol and 22-oxacalcitriol into the parathyroid gland causes enhancement of the cellular apoptosis and reduce the parathyroid hyperplasia. Newer therapies
Selective percutaneous ethanol injection therapy and direct injection with active vitamin D compounds such as calcitriol and 22-oxacalcitriol into the parathyroid gland causes enhancement of the cellular apoptosis and reduce the parathyroid hyperplasia.
Parathyroidectomy If the PTH levels remains >1000 pg/ml with hypercalcemia even after medical therapy or when the volume of gland is >500 mm3, surgery is recomended. Parathyroidectomy
If the PTH levels remains >1000 pg/ml with hypercalcemia even after medical therapy or when the volume of gland is >500 mm3, surgery is recomended.

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