Secondary hyperparathyroidism is the excess production of the parathyroid glands due to another condition that does not lie in the glands themselves, such as decreased calcium levels, vitamin D deficiency, or chronic renal failure.
The clinical features will reflect the etiology of the condition. Patients with severe cases of hypocalcemia and vitamin D deficiency will suffer from neuromuscular symptoms, including paresthaesia in the fingers, toes, or around the mouth; muscle cramps; tetany; seizures; or laryngospasm .
Vitamin D deficiency results in abnormal mineralization of the bone, which manifests as bowed legs or knocked knees in children. In adults, skeletal deformities rarely occur because of the sufficient bone mineralization. They may however suffer from a condition known as osteomalcia. Muscle weakness or pain may be the only symptom in less-severe cases of vitamin D deficiency.
Two main signs may be elicited by physical examination. The first one is twitching of muscles around the mouth when tapping on the face anterior to the ear, which is called Chvostek's sign. The second one is called Trousseau's sign, which is defined as muscular flexion of the wrist, hyperextension of the fingers, and flexion of the thumb due to inflating a blood-pressure cuff above diastolic for 3 minutes.
Signs and symptoms of chronic kidney disease may be seen in patients who have the condition, which includes bruising and skin discoloration, pruritus, pericardial rub, edema, fatigue, nausea, lung rales, myoclonus, and poor level of concentration.
Different conditions, such as celiac disease, Crohn disease, chronic pancreatitis, Whipple disease, or following gastric bypass surgery may result in malabsorption, which in return leads to vitamin D deficiency and poor absorption of calcium . Symptoms and signs of these conditions may be observed in patients suffering from these conditions, including abdominal pain, changes in bowel habits, and chronic diarrhea.
Entire Body System
- Increased Energy
However, recent translational work has provided compelling evidence for a causal role of parathyroid hormone (PTH) in the pathogenesis of adipose tissue browning and increased energy expenditure, a critical component of PEW in ESRD. [ncbi.nlm.nih.gov]
Nausea, vomiting and hypocalcaemia are commonly experienced by patients treated with cinacalcet. [doi.org]
Cinacalcet increases risks of nausea, vomiting and hypocalcaemia, suggesting harms may outweigh benefits in this population. Read the full abstract... [cochrane.org]
DIAGNOSES: The patient ate some recently pickled vegetables, and he experienced nausea, vomiting and diarrhoea without oliguria or anuria; Additionally, his hands and both forearms had a typical blue ash appearance. [ncbi.nlm.nih.gov]
The clinical features include neuromuscular symptoms, bone pain and bowing in children due to vitamin D deficiency, and other signs related to the chronic kidney disease such as edema, fatigue and nausea. [symptoma.com]
Also tell your healthcare provider if you have nausea or vomiting that is getting worse. [sensipar.com]
- Abdominal Pain
pain), "stones" (kidney), "bones" (bone pain), and "psychiatric overtones" (confusion, altered mental state, lethargy, depression, fatigue). [flexikon.doccheck.com]
Symptoms include: Kidney stones Excessive urination Abdominal pain Tiring easily or weakness Depression or forgetfulness Frequent complaints of illness with no apparent cause Nausea, vomiting or loss of appetite Bone deformities, fractures and swollen [kidneyresearchuk.org]
Excess PTH causes GI symptoms like nausea, vomiting, abdominal pain, and loss of appetite. Finally, the psychic groans of the saying stem from hypercalcemia's effect on neurotransmitters. This can cause symptoms like depression and memory problems. [study.com]
The range of signs and symptoms include: Fragile bones that easily fracture (osteoporosis) Kidney stones Excessive urination Abdominal pain Tiring easily or weakness Depression or forgetfulness Bone and joint pain Frequent complaints of illness with no [mayoclinic.org]
Symptoms and signs of these conditions may be observed in patients suffering from these conditions, including abdominal pain, changes in bowel habits, and chronic diarrhea. [symptoma.com]
- Chronic Diarrhea
diarrhea, or ileostomy no calcimimetic or active vitamin D therapy 30 days prior to enrollment use of digoxin, magnesium containing products, mineral oil, or cholestyramine Information from the National Library of Medicine To learn more about this study [clinicaltrials.gov]
Symptoms and signs of these conditions may be observed in patients suffering from these conditions, including abdominal pain, changes in bowel habits, and chronic diarrhea. [symptoma.com]
Osteopenia or osteoporosis was not present. [edmcasereports.com]
Denosumab, an anti-resorptive treatment for osteoporosis and skeletal metastases from solid tumours, can cause hypocalcaemia. The incidence may be higher than previously reported due to varying serum calcium cut-off and timing of measurement. [ncbi.nlm.nih.gov]
Soon after the PAIT, his arthralgia disappeared. Serum PTH fell to 220 pg/ml with the regression of bone marker 1 year following the PAIT. The size of his parathyroid glands dramatically regressed and 1 of the enlarged glands finally disappeared. [ncbi.nlm.nih.gov]
[…] vision, insomnia, lethargy, weakness Possible diagnoses: corneal calcification, delirium, mild cognitive impairment Renal Polydipsia, polyuria, renal colic Possible diagnoses: nephrocalcinosis, nephrolithiasis, nephrogenic diabetes insipidus Skeletal Arthralgia [aafp.org]
- Rachitic Rosary
These diseases typically present in childhood with the classic physical examination finding of nutritional rickets, such as genu varum/valgum and rachitic rosary. [ncbi.nlm.nih.gov]
On examination, she had a short stature (146 cm), frontal bossing of the cranium, bulging of the costochondral junctions (rachitic rosary) and bowing of the lower limbs. [pubs.sciepub.com]
- Knee Pain
Abstract A 48-year-old male was admitted to our hospital because of increasing knee pain and thigh muscle weakness. He had been undergoing hemodialysis for 15 years. [ncbi.nlm.nih.gov]
Face, Head & Neck
- Neck Swelling
After 2 years of parathyroidectomy, the neck swelling again started increasing in size with increase in serum parathormone levels. [ncbi.nlm.nih.gov]
Laboratory studies in suspected patients include measuring serum levels of PTH, calcium, phosphorus, and 25-hydroxyvitamin D  . In patients with secondary hypperparathyroidism, high levels of PTH and decreased levels of calcium will be observed.
Vitamin D levels are measured through its bioactive form (25-hydroxyvitamin D) levels. Results more 30 ng per milliliter are considered normal; however, levels less than 20 ng per milliliter indicate vitamin D deficiency.
Serum level of phosphate will differ depending on the underlying etiology. In vitamin D deficiency cases, the levels will be low; contrary to kidney disease that presents with high levels.
Imaging studies may be used to assess bone disease. However, they are not indicated for parathyroid glands unless primary hyperparathyroidism is suspected .
This study shows that the A allele of rs7652589 is a risk allele for nephrolithiasis-related ESRD. The AA genotype is associated with more severe sHPT (higher Ca and PTH concentrations). [ncbi.nlm.nih.gov]
Evidence of nephrolithiasis or nephrocalcinosis via imaging Reduced bone mineral density ( T-score < -2.5 at lumbar spine, total hip, femoral neck, or distal third of the radius, or preexisting asymptomatic vertebral fracture ) The procedure depends [amboss.com]
PHPT must always be evaluated in patients with clinical histories of nephrolithiasis, nephrocalcinosis, osseous pain, subperiosteal resorption, and pathologic fractures, as well as in those with osteoporosis–osteopenia, a personal history of neck irradiation [reumatologiaclinica.org]
Patients with primary hyperparathyroidism, the most common cause of hypercalcemia in outpatients, are often asymptomatic or may have bone disease, nephrolithiasis, or neuromuscular symptoms. [aafp.org]
Presence of nephrolithiasis or nephrocalcinosis as determined using radiography, ultrasonography, or CT scanning Age younger than 50 years Some clinicians advocate surgical therapy in all patients with primary hyperparathyroidism, modified only for those [emedicine.medscape.com]
- Ground Glass Appearance
Increased cortical density is a rare manifestation of secondary hyperparathyroidism, which normally causes the lamina dura to vanish and produces a ground-glass appearance as a result of blurring of the trabecular bone pattern. [ncbi.nlm.nih.gov]
Secondary hyperparathyroidism is usually treated medically with no need for surgical intervention. The recommended medical treatment depends on the etiology of the condition.
In patients with vitamin D deficiency, vitamin D-2 can be used once a week for 8 weeks to achieve sufficient levels of vitamin D. The course may be repeated if needed.
There are different nonsurgical options to treat chronic kidney disease cases, including:
- Dietary phosphate should be restricted if parathyroid hormone is elevated in spite of sufficient levels of vitamin D .
- If phosphate levels are still increased after dietary restriction, phosphate binders may be used. Such include calcium carbonate, lanthanum carbonate, calcium acetate, or sevelamer hydrochloride .
- Calcium supplements should be lower than 2 g per day.
Other vitamin D analogs can be applied, such as calcitriol, paricalcitol, doxercalciferol, maxacalcitol, or falecalcitriol. Biochemical parameters have shown significant improvements in treatment with cinacalcet and other calcimimetics.
Usually, medical treatment suffices and surgical intervention is not required; however, surgery may be indicated if there was bone pain or fracture, pruritus, calciphylaxis, or extraskeletal nonvascular calcifications accompanied by high levels of PTH in spite of medical treatment .
Patients with severe persistent hyperparathyroidism with hypercalcemia and high levels of phosphate may require parathyroidectomy if medical treatment proves not successful.
Medical treatment is successful in most secondary hyperparathyroidism patients. There is a 10% risk of recurrence in patients who require parathyroidectomy. This is usually due to a hyper-functioning or missed gland or autograft hyperplasia. Some patients develop hypoparathyroidism after parathyroidectomy, which is usually reversed by transplantation or lifelong calcium and calcitriol supplementation in permanent cases.
In secondary hyperparathyroidism, the calcium levels are lower than normal due to an underlying condition that leads to overproduction of parathyroid hormone.
Different factors may contribute to the developing of this condition. In case of severe calcium deficiency the diet does not provide sufficient calcium for the body, or the digestive system is not able to withdraw the calcium from the diet . Another factor is vitamin D deficiency. Vitamin D is important to achieve normal blood levels of calcium, it also helps in the absorption of calcium through the digestive system. Sunlight exposure is required for the body in order to produce vitamin D. Calcium levels will drop in cases of severe vitamin D deficiency. Vitamin D is converted into the usable bioactive form by the kidneys, which makes chronic kidney failure the most common cause of secondary hyperparathyroidism .
Chronic kidney failure and vitamin D deficiency are usually associated with secondary hyperparathyroidism. In the United States, it is estimated that low levels of 25-hydroxyvitamin D (the bioactive form of vitamin D) are found in 6% of the population (levels less than 25 nanomol/L) . The incidence is even higher among non-Hispanic black people as it was estimated 29% in 2004 .
Chronic kidney disease is diagnosed in 26 million American adults with millions of people at increased risk of vitamin D deficiency and secondary hyperparathyroidism. Dialysis-dependent chronic failure patients will eventually develop secondary hyperparathyroidism.
There are four parathyroid glands located on the thyroid gland, each one of them has the size of a pea. They play an important role in maintaining the balance of calcium and phosphorus in the body through secreting the parathyroid hormone. This hormone is involved in the release of calcium from bone and its absorption from the intestine, which regulates its levels in the blood. The secretion of PTH by the thyroid glands is affected by the blood levels of calcium, phosphorus and vitamin D.
In chronic kidney disease, an increase in phosphorus excretion and a decrease in the levels of vitamin D, which is required for calcium absorption, can be observed. These changes result in an increase of PTH secretion from the parathyroid glands leading to secondary hyperparathyroidism .
Prevention of secondary hyperparathyroidism is achieved through the avoidance of the causing etiologies. Chronic kidney disease is prevented through aggressive management of hypertension, diabetes, and other conditions that predispose to kidney injury.
Adequate replacement of vitamin D with aggressive phosphorus management is required early in cases of chronic renal failure in order to avoid the development of secondary hyperparathyroidism .
Decreasing phosphorus intake and the use of phosphorus-binding drugs help in the prevention of secondary hyperparathyroidism. However, phosphorus binders containing aluminium are not recommended because of their toxicity to the skeleton .
Exposure to sunlight at least 5 to 30 minutes twice a week prevents vitamin D deficiency, which is one of the main etiologies for the development of secondary hyperparathyroidism .
Secondary hyperparathyroidism may develop due to different etiologies, including decreased kidney function, vitamin D deficiency or failure to activate its bioactive form, and impaired phosphate excretion. These changes result in dysregulation of calcium and phosphorus homeostasis, which leads to increased levels of serum phosphorus and phosphatonin fibroblast growth factor 23 (FGF-23), as well as decreased synthesis of the active form of vitamin D. This results in parathyroid hyperplasia and overproduction of the parathyroid hormone (PTH) from the parathyroid glands .
The clinical features include neuromuscular symptoms, bone pain and bowing in children due to vitamin D deficiency, and other signs related to the chronic kidney disease such as edema, fatigue and nausea.
Parathyroid hormone, calcium, and phosphorus levels are measured using laboratory studies. Examination will reveal high levels of the parathyroid hormone and different levels of calcium and phosphorus depending on the underlying etiology. Radiographic studies may be used to evaluate bone damage and involvement; however, they are rarely used for the parathyroid glands themselves in cases of secondary hyperparathyroidism.
Secondary hyperparathyroidism is usually treated medically with no need for surgical intervention, except in cases of medical treatment failure, where parathyroidectomy may be considered as an option.
The prognosis is good in patients who are managed successfully with medical treatment. Patients who undergo parathyroidectomy carry a 10% risk of recurrence.
The parathyroid glands are four small pea-sized glands found directly on the thyroid gland. These four glands secrete an important hormone called parathyroid hormone (PTH), which is essential in the maintenance of normal calcium levels within the body.
Increased production of the parathyroid hormone may be due to a problem within the parathyroid glands, which is called primary hyperparathyroidism. Another cause is a condition that affects the parathyroid glands and results in overproduction of the hormone, this is called secondary hyperparathyroidism.
Secondary hyperparathyroidism usually results from any condition that leads to decreased levels of calcium in the blood. The most common cause is chronic kidney disease. Also decreased levels of vitamin D due to malabsorption or the lack of exposure to sunlight can be a factor.
In cases of chronic kidney disease, the blood levels of phosphorus are increased and the kidney is not able to convert vitamin D into its active form, which is important for the absorption of calcium. If parathyroid glands fail to correct the blood levels of calcium, a condition called hypocalcaemia may occur, which means decreased levels of calcium. This may lead to neuromuscular symptoms and features, such as weakness, muscle cramps, or seizures. In cases of chronic kidney disease, its symptoms will also be noticed including fatigue, edema, discoloration, and nausea.
Vitamin D deficiency may result in bone pain, weakening or bowing, especially in children.
Simple blood tests are used to diagnose secondary hyperparathyroidism, which will reveal normal or low levels of calcium, low or high levels of phosphate, and increased levels of PTH. Imaging studies, such as x-rays, may be used to evaluate bone disease.
The management of secondary hyperparathyroidism involves the correction of the underlying cause, for example, chronic kidney disease or vitamin D deficiency. If simple medical treatment proves not effective, other medications called calcimimetics may be used. Severe persistent cases of the condition that do not respond to medical treatment may require surgical removal of the parathyroid glands.
The outcome is good after successful medical treatment. However, patients who undergo surgical removal of the glands may have a risk of recurrence.
Prevention of the etiologic conditions will decrease the risk of developing secondary hyperparathyroidism.
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