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Hypercalcemia

Pathological Hypercalcemia

Hypercalcemia is the presence of an abnormally high concentration of calcium in the blood.


Presentation

The symptoms and signs of hypercalcemia are now more often mild and general rather than severe renal and bone problems seen years ago:
GENERAL -symptoms such as malaise and depression
RENAL- renal colic from stones, polyuria/ nocturia, haematuria and hypertension.
BONES-bone pain.
ABDOMINAL-abdominal pain due to peptic ulceration.
In malignant diseases, hypercalcemia results from bony metastasis which indicates the malignant disease is of longstanding duration. Severe hypercalcemia is usually associated with malignant disease, hyperparathyroidism, renal dialysis or vitamin D therapy.
Corneal calcification is a marker of longstanding hypercalcemia. In primary hyperparathyroidism, only 5-10% have definite bony lesions and 20-40% renal involvement.
In longstanding cases of hypercalcemia, calcium starts getting deposited in soft tissues or can lead to renal stone formation.

Fatigue
  • A 39-year-old woman was admitted to our hospital with symptoms of general fatigue, nausea, and vomiting that appeared three months after she stopped seven years of medroxyprogesterone acetate (MPA) medication for endometrial stromal sarcoma.[ncbi.nlm.nih.gov]
  • Here we present the case of an infant with hypercalcemia who presented with fatigue, irritability, and failure to thrive after prolonged immobilization.[ncbi.nlm.nih.gov]
  • Here, we report the case of a previously healthy 3-year-old who was admitted to the emergency room with fatigue, hyporeactivity, fever and limping gait that had evolved over 5 days and that was progressively worsening.[ncbi.nlm.nih.gov]
  • We report on 3 cases of life-threatening hypercalcemia revealing florid and isolated acute sarcoid-like myositis.All patients complained of fatigue, progressive general muscle weakness, and weight loss.[ncbi.nlm.nih.gov]
  • A previously healthy 24 yo male presented with a two-month history of epigastric pain, nausea, vomiting, fatigue and malaise.[ncbi.nlm.nih.gov]
Prolonged Immobilization
  • Therefore, they are prone to the imbalance of osteoblastic and osteoclastic activity that occurs with prolonged immobilization, leading to hypercalcemia.[ncbi.nlm.nih.gov]
  • Kidney failure, adrenal gland failure, hyperthyroidism, prolonged immobilization, use of a class of diuretics called thiazides, and ingestion of massive amounts of calcium (milk-alkali syndrome) are other potential hypercalcemia causes.[raysahelian.com]
  • Kidney failure, adrenal gland failure, hyperthyroidism, prolonged immobilization, use of a class of diuretics called thiazides, and ingestion of massive amounts of calcium (milk-alkali syndrome) are other potential causes.[uclahealth.org]
  • immobilization, dietary, iatrogenic) Clinical Manifestations “Stones (renal), Bones (bone pain), Groans (abdominal pain) Moans (Psychiatric overtones)” Cardiac Effects Bradydysrhythmias AV block Sinus Arrest Atrial Fibrillation Ventricular Tachycardia[coreem.net]
  • immobilization Paget's disease Thiazide use Vitamin A intoxication Kidney failure [ edit ] Severe secondary hyperparathyroidism Tertiary hyperparathyroidism Aluminium intoxication Milk-alkali syndrome Other [ edit ] Adrenal insufficiency Zollinger Ellison[en.wikipedia.org]
Hodgkin's Disease
  • Calcitriol: the major humoral mediator of hypercalcemia in Hodgkin's disease and non-Hodgkin's lymphomas. Blood . 1993; 82 (5):1383-1394. [PubMed] 10 Overbergh L, Decallonne B, Valckx Det al.[jaoa.org]
  • Calcitriol: the major humoral mediator of hypercalcemia in Hodgkin's disease and non-Hodgkin's lymphomas . Blood 1993; 82 : 1383–1394. 5. Burtis WJ , Brady TG , Orloff JJ , Ersbak JB , Warrell Jr RP , Olson BR et al .[nature.com]
Poor Feeding
  • We report a 4-day-old infant who presented with hyperbilirubinemia, poor feeding, weight loss, severe hypotonia and was ultimately diagnosed with NSHPT.[ncbi.nlm.nih.gov]
Nausea
  • A 39-year-old woman was admitted to our hospital with symptoms of general fatigue, nausea, and vomiting that appeared three months after she stopped seven years of medroxyprogesterone acetate (MPA) medication for endometrial stromal sarcoma.[ncbi.nlm.nih.gov]
  • She complained of severe myalgias, arthralgias, an inability to ambulate, nausea, vomiting, abdominal pain, and marked depression.[ncbi.nlm.nih.gov]
  • She had nausea, vomiting, leg pain, polyuria, polydipsia, and muscle weakness. At the time of relapse, the ionized calcium level was 1.99 mmol/L.[ncbi.nlm.nih.gov]
  • Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder.[ncbi.nlm.nih.gov]
  • A previously healthy 24 yo male presented with a two-month history of epigastric pain, nausea, vomiting, fatigue and malaise.[ncbi.nlm.nih.gov]
Vomiting
  • A 39-year-old woman was admitted to our hospital with symptoms of general fatigue, nausea, and vomiting that appeared three months after she stopped seven years of medroxyprogesterone acetate (MPA) medication for endometrial stromal sarcoma.[ncbi.nlm.nih.gov]
  • She complained of severe myalgias, arthralgias, an inability to ambulate, nausea, vomiting, abdominal pain, and marked depression.[ncbi.nlm.nih.gov]
  • She had nausea, vomiting, leg pain, polyuria, polydipsia, and muscle weakness. At the time of relapse, the ionized calcium level was 1.99 mmol/L.[ncbi.nlm.nih.gov]
  • Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder.[ncbi.nlm.nih.gov]
  • A previously healthy 24 yo male presented with a two-month history of epigastric pain, nausea, vomiting, fatigue and malaise.[ncbi.nlm.nih.gov]
Constipation
  • Symptoms of hypercalcemia include lethargy, mental imbalance, weakness, dehydration, constipation, nausea, diarrhea, and even heart arrhythmia. [ 1 ] When chronic constipation is associated with thyroid disorders, it is often attributable to hypercalcemia[globalhealingcenter.com]
  • Patients with more-severe hypercalcemia may have nausea, vomiting, weight loss, constipation, Read More In human endocrine system: Ectopic hormone and polyglandular disorders …abnormal hormone-related physiological conditions, including hypercalcemia[britannica.com]
  • Common symptoms of hypercalcemia include: Fatigue (tired feeling) Excessive sleepiness Confusion Coma Extreme muscle weakness Loss of appetite Nausea, vomiting Stomach pain Constipation Changes in heartbeat (too slow or too fast) Frequent urination Excessive[northwell.edu]
  • […] to rapid bone turnover 6) Hyperthyroidism – causes increase in bone resorption Clinical Manifestations of Hypercalcemia: Neuro changes: confusion, ams, coma Psychosis GI ulcers (calcium increases gastric secretion) abdominal pain, nausea and vomiting constipation[errolozdalga.com]
  • Definition (CSP) abnormally high level of calcium in the blood; manifestations include fatigability, muscle weakness, depression, anorexia, nausea, and constipation.[fpnotebook.com]
Abdominal Pain
  • She complained of severe myalgias, arthralgias, an inability to ambulate, nausea, vomiting, abdominal pain, and marked depression.[ncbi.nlm.nih.gov]
  • Bob R is a 67 year-old man who presents to the emergency department with increasing abdominal pain and vomiting. His wife says he has been more confused over the past few days. Amongst other blood tests, his calcium returns at 3.2 mmol/L.[sharinginhealth.ca]
  • Symptoms can appear intermittently and vary greatly; they might include nausea, vomiting, indeterminate abdominal pain, constipation, and kidney failure.[globalhealingcenter.com]
  • pain, nausea and vomiting constipation kidney stones, renal failure pancreatitis polyuria, polydypsia (Calcium induced Diabetes insipidus) bradycardia AV block short qt Management: 1.[errolozdalga.com]
  • pain Difficulty concentrating and memory problems Itching Diagnosis Your doctor will ask about your symptoms and medical history and perform a physical exam.[uvahealth.com]
Polydipsia
  • She had nausea, vomiting, leg pain, polyuria, polydipsia, and muscle weakness. At the time of relapse, the ionized calcium level was 1.99 mmol/L.[ncbi.nlm.nih.gov]
  • CASE REPORT A 58-year-old male with a past medical history of CML diagnosed six years earlier, presented to the emergency department with one week of acute confusion, disorientation, polyuria, and polydipsia.[ncbi.nlm.nih.gov]
  • Case Report A 63 year old Mexican man with history of advanced prostatic adenocarcinoma and trans-urethral resection of prostate presented to ER with nausea, vomiting, polydipsia and altered mental status.[pubs.sciepub.com]
  • History may also identify symptoms of high calcium such as renal stones typical of hyperparathyroidism, or lethargy, easy fatigue, confusion, depression, irritability, constipation, and polyuria and polydipsia.[us.bestpractice.bmj.com]
  • Signs : may include anorexia, lethargy, weight loss, poor performance, depression, sometimes polyuria/polydipsia, and other signs dependant upon cause.[vetstream.com]
Hypertension
  • Common medications such as hydrochlorothiazide and other thiazide diuretics (prescribed for hypertension and edema ), lithium, and excessive intake of vitamin D, vitamin A or calcium can result in hypercalcemia.[my.clevelandclinic.org]
  • Question I have 66 year old lady with PHM Diabetes type II, obesity and hypertension. Referred by her GP with corrected Calcium mildly high at 2.68nmol/l (2.2-2.6), phosphate 1.07nmol/L , ALP normal PTH 6.2(1.1-6.9) as query hyperparathyroidism.[endotext.org]
  • We seem to be diagnosing raised Ca more in asymptomatic patients or in the work-up for other common problems eg. osteoporosis, hypertension, depression Bone pain may be general and non-specific, related to underlying aetiology eg. myeloma, metastatic[broomedocs.com]
  • Skeletal Fractures Osteoporosis Bone cysts Kidney Nephrocalcinosis (calcification of the kidney) Kidney stones Dehydration Kidney failure Gastrointestinal Pancreatitis Peptic ulcer disease Hypertension Psychosocial Difficulty concentrating or thinking[uclahealth.org]
  • The patient had a medical history of hypertension and osteoporosis and had undergone an appendectomy as a child. Her mother had died of breast cancer in her 30s, and her father had had melanoma.[jaoa.org]
Muscle Weakness
  • She had nausea, vomiting, leg pain, polyuria, polydipsia, and muscle weakness. At the time of relapse, the ionized calcium level was 1.99 mmol/L.[ncbi.nlm.nih.gov]
  • We report on 3 cases of life-threatening hypercalcemia revealing florid and isolated acute sarcoid-like myositis.All patients complained of fatigue, progressive general muscle weakness, and weight loss.[ncbi.nlm.nih.gov]
  • Common symptoms of hypercalcemia include: Fatigue (tired feeling) Excessive sleepiness Confusion Coma Extreme muscle weakness Loss of appetite Nausea, vomiting Stomach pain Constipation Changes in heartbeat (too slow or too fast) Frequent urination Excessive[northwell.edu]
  • Definition (CSP) abnormally high level of calcium in the blood; manifestations include fatigability, muscle weakness, depression, anorexia, nausea, and constipation.[fpnotebook.com]
  • weakness Constipation Nausea and vomiting Irregular heartbeat Fatigue Appetite loss and weight loss Abdominal pain Difficulty concentrating and memory problems Itching Diagnosis Your doctor will ask about your symptoms and medical history and perform[uvahealth.com]
Polyuria
  • She had nausea, vomiting, leg pain, polyuria, polydipsia, and muscle weakness. At the time of relapse, the ionized calcium level was 1.99 mmol/L.[ncbi.nlm.nih.gov]
  • CASE REPORT A 58-year-old male with a past medical history of CML diagnosed six years earlier, presented to the emergency department with one week of acute confusion, disorientation, polyuria, and polydipsia.[ncbi.nlm.nih.gov]
  • A hypercalcemia state interferes with the action of ADH hormone on the distal tubule causing a state of nephrogenic diabetes insipidus resulting in polyuria.[symptoma.com]
  • […] increase in bone resorption Clinical Manifestations of Hypercalcemia: Neuro changes: confusion, ams, coma Psychosis GI ulcers (calcium increases gastric secretion) abdominal pain, nausea and vomiting constipation kidney stones, renal failure pancreatitis polyuria[errolozdalga.com]
  • […] due to promotion of renal clearance thru osmotic diuresis) Thirst, dehydration (due to polyuria and renal impairment causing water reabsorption) Constipation due to polyuria which leads to dehydration and hypercalcemia causing a raised action potential[acidicbody.com]
Nocturia
  • Lethargy, thirst, polyuria, and nocturia developed in a 34-year-old woman who was 35 weeks pregnant. Physical examination was normal.[nejm.org]
  • The symptoms and signs of hypercalcemia are now more often mild and general rather than severe renal and bone problems seen years ago:GENERAL -symptoms such as malaise and depression RENAL- renal colic from stones, polyuria/ nocturia, haematuria and hypertension.BONES-bone[symptoma.com]
  • Impairment of the renal concentrating mechanism leads to polyuria, nocturia, and polydipsia. Elevation of serum calcium 12 mg/dL ( 3.00 mmol/L) can cause emotional lability, confusion, delirium, psychosis, stupor, and coma.[merckmanuals.com]
  • If renal impairment occurs as a result, manifestations can include polyuria , nocturia , and polydipsia . [6] Psychiatric manifestation can include emotional instability, confusion , delirium , psychosis , & stupor . [6] Limbus sign seen in eye due to[en.wikipedia.org]
Psychiatric Manifestation
  • If renal impairment occurs as a result, manifestations can include polyuria , nocturia , and polydipsia . [6] Psychiatric manifestation can include emotional instability, confusion , delirium , psychosis , & stupor . [6] Limbus sign seen in eye due to[en.wikipedia.org]
Lethargy
  • We report a case of a 39-year-old female with active systemic lupus erythematosus who complained of lethargy and weakness with a moderate renal impairment. Hypercalcemia was confirmed by laboratory examination.[ncbi.nlm.nih.gov]
  • Although irritability and lethargy were commonly reported, no mortality or acute life-threatening events were associated with hypercalcemia and the only statistically associated morbidities were dehydration, hypercalciuria, and nephrocalcinosis.[ncbi.nlm.nih.gov]
  • Although having symptoms of hypercalcemia is uncommon, symptoms can include: More frequent urination and thirst Fatigue, bone pain, headaches Nausea, vomiting , constipation , decrease in appetite Forgetfulness Lethargy, depression , memory loss or irritability[my.clevelandclinic.org]
  • History may also identify symptoms of high calcium such as renal stones typical of hyperparathyroidism, or lethargy, easy fatigue, confusion, depression, irritability, constipation, and polyuria and polydipsia.[us.bestpractice.bmj.com]
  • , Bones (bone pain), Groans (abdominal pain) Moans (Psychiatric overtones)” Cardiac Effects Bradydysrhythmias AV block Sinus Arrest Atrial Fibrillation Ventricular Tachycardia QTc shortening Neuropsychiatric Disorders Major: AMS, seizures, weakness, lethargy[coreem.net]
Irritability
  • Here we present the case of an infant with hypercalcemia who presented with fatigue, irritability, and failure to thrive after prolonged immobilization.[ncbi.nlm.nih.gov]
  • Although irritability and lethargy were commonly reported, no mortality or acute life-threatening events were associated with hypercalcemia and the only statistically associated morbidities were dehydration, hypercalciuria, and nephrocalcinosis.[ncbi.nlm.nih.gov]
  • History may also identify symptoms of high calcium such as renal stones typical of hyperparathyroidism, or lethargy, easy fatigue, confusion, depression, irritability, constipation, and polyuria and polydipsia.[us.bestpractice.bmj.com]
  • Although having symptoms of hypercalcemia is uncommon, symptoms can include: More frequent urination and thirst Fatigue, bone pain, headaches Nausea, vomiting , constipation , decrease in appetite Forgetfulness Lethargy, depression , memory loss or irritability[my.clevelandclinic.org]
  • Although calcium is necessary for bone health and proper heart function, too much calcium in your blood can cause symptoms such as gastrointestinal problems, irritability, bone pain and increased risk of fracture.[livestrong.com]
Altered Mental Status
  • On physical examination, we observed tachycardia, altered mental status, and dehydration. Blood analysis revealed leukocytosis, thrombocytosis, and marked hypercalcemia (18.6 mg/dL).[ncbi.nlm.nih.gov]
  • Patients with a performance status 2, altered mental status, C-reactive protein 30 mg/L, albumin 2.5 g/dL, or body mass index 18 kg/m2 had significantly poorer survival in a univariable analysis, and longer OS was related to treatment-naive patients,[ncbi.nlm.nih.gov]
  • Ten days later while in rehabilitation, he started complaining of progressive fatigue and altered mental status was noted. He was found to have a calcium level of 15.5 and was admitted to the intensive care unit for management and further workup.[ncbi.nlm.nih.gov]
  • Postpartum, she developed severe hypercalcemia (14 mg/dL), altered mental status, and acute pancreatitis. Her PTH was suppressed (6 pg/mL) and her 1,25(OH)2 D was elevated (165 and 195 pg/mL on postpartum day 1 and 5, respectively).[ncbi.nlm.nih.gov]
  • Case Report A 63 year old Mexican man with history of advanced prostatic adenocarcinoma and trans-urethral resection of prostate presented to ER with nausea, vomiting, polydipsia and altered mental status.[pubs.sciepub.com]
Stupor
  • The sluggish nerves also explain drowsiness , confusion, hallucinations, stupor and / or coma. In the gut this causes constipation .[en.wikipedia.org]
  • Elevation of serum calcium 12 mg/dL ( 3.00 mmol/L) can cause emotional lability, confusion, delirium, psychosis, stupor, and coma. Hypercalcemia may cause neuromuscular symptoms, including skeletal muscle weakness.[merckmanuals.com]
Mild Cognitive Impairment
  • Presentation of Hypercalcaemia At levels At levels At levels 3.5 mmol/L Polyuria and polydipsia Dyspepsia - due to calcium-regulated release of gastrin Depression Mild cognitive impairment All of the previous plus: Muscle weakness Constipation Anorexia[patient.info]

Workup

Diagnosing the cause of hypercalcemia requires a complete physical history and examination which is a more complex process. [9]
Several fasting serum calcium and phosphate samples should be taken. Hypophosphataemia is common in primary hyperparathyroidism. If calcium levels are mildly elevated since long, malignancy is not likely to be the cause. Sudden onsets of elevated levels of calcium are suspected for malignancies. Most likely malignancies could be breast, lung, kidney multiple myeloma, lymphoma or leukaemias. Serum PTH levels should be measured; if high during hypercalcemia it definitely implies hyperparathyroidism.

Abdominal X-Rays show renal calculi or nephrocalcinosis. Renal function must be measured. Chest X-Ray should be done to rule out chest malignancies or sarcoidosis. Biopsy may also be done for sarcoidosis. Proteins electrophoresis should be done to confirm for myeloma. Serum TSH, T3 are necessary to diagnose underlying thyrotoxicosis. PTH reduces renal tubular reabsorption of bicarbonate, thus bicarbonate levels fall and plasma chloride levels rise in primary hyperparathyroidism.
If hyperparathyroidism is confirmed, the following tests may be useful in localization although adenomas are usually small-
Ultrasound for tumors
CT or MRI scans for better viewing and resolution.
Barium swallow may show indention of esophagus by adenoma.

Nephrolithiasis
  • Mutations of the CYP24A1 gene, encoding for the enzyme 25(OH)D-24-hydroxylase, can cause hypercalcemia, hypercalciuria, nephrolithiasis and nephrocalcinosis.[ncbi.nlm.nih.gov]
  • We herein present a case of relapsed sarcoidosis with a deteriorated renal function accompanied by hypercalcemia, nephrolithiasis, and a ureteral stone in a woman with a history of ocular sarcoidosis.[ncbi.nlm.nih.gov]
  • Hypercalcemia can result in nephrocalcinosis/nephrolithiasis and may lead to renal failure. Idiopathic infantile hypercalcemia is caused by mutations of the CYP24A1 gene, which regulates vitamin D activity.[ncbi.nlm.nih.gov]
  • Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis[ncbi.nlm.nih.gov]
  • Loss-of-function mutations in CYP24A1 cause hypercalcemia, nephrolithiasis and nephrocalcinosis. We describe a woman with CYP24A1 deficiency and recurrent gestational hypercalcemia.[ncbi.nlm.nih.gov]
Microcytic Anemia
  • Laboratory tests indicated severe hypercalcemia (total calcium 21.39mg/dL, ionized calcium 2.93mmol/L) and microcytic anemia. Hyperhydration was initiated, and the child was transferred to the pediatric intensive care unit.[ncbi.nlm.nih.gov]
Short QT Interval
  • QT Interval - LITFL Short QT Interval - LITFL Management Supportive Care – ABCs, IV, O 2 , Monitor Volume Expansion The majority of patients with hypercalcemia have significant dehydration Normal saline administration Mechanism of action: Corrects volume[coreem.net]
  • QT interval [16] suggest hypercalcaemia.[en.wikipedia.org]

Treatment

The main aim of treatment is first to bring down the levels of calcium followed by treating the underlying medical condition responsible for hypercalcemia. [10]
Hydration is very important as dehydration due to vomiting or renal impairment result in concentrated urine. An increased uptake of salt can help in increased excretion of sodium following increased potassium excretion. A loop diuretic can be give to sustain salt and water replacement preventing fluid overload. In addition loop diuretics also have inhibitory action on the calcium renal resorption. Thus, this helps, to further lower the calcium levels. With this treatment calcium levels can be bought down by 1-3 mg/dl within 24 hours. Caution should be taken to prevent magnesium or potassium depletion.

Second line of treatment includes biphosphonates [11] and calcitonin therapy. Bisphosphonates are taken by osteoclasts and prevent bone resorption. Bisphosphonates are contraindicated in renal failure patients. Calcitonin also prevents bone resorption and increases urinary excretion of calcium.

All cancer patients should receive bisphosphonates as the first line of treatment may not be possible to complete without any risks and side effects. Recurrence of hypercalcemia in such patients is inevitable.
Other therapies include use of glucocorticoids. Dialysis may be opted for in severe cases with renal failure. Supplementary phosphate therapy is recommended in case of low phosphate levels.

Indications for surgery in hyperparathyroidism remain controversial, but if needed should be done by a qualified surgeon. All agree that with renal disease or bone involvement, since there is no long term treatment requires surgery. Main complication of surgery is hypocalcaemia which should be carefully monitored.

Prognosis

The outlook of hypercalcemia mainly depends on the cause. Mild cases of hyperparathyroidism or hypercalcemia with a treatable cause have a good prognosis. Most cases have no complications at all.
Malignancies or granulomatous diseases associated with hypercalcemia usually do not do well, which is majorly due the underlying disease rather than hypercalcemia. The usual 30 day survival in malignancies is about 50%. Many cases of malignancies [8] in final stage show hospitalization due to an emergency. Thus mortality and morbidity mainly depend on the cause and are basically a reflection of how well the disease is treated or under control.

Etiology

Major causes are primary hyperparathyroidism and malignancies. Hyperparathyroidism is the commonest cause. Other causes of hypercalcemia can be listed as follows

1. BONY RESORPTIVE HYPERCALCEMIA

  • Excess PTH- primary hyperparathyroidism [3]. Primary hyperparathyroidism is very frequent in women above the age of 50. Primary hyperparathyroidism can occur when all the four parathyroid glands produce too much of PTH or one single gland starts producing an excess of PTH mainly due to an adenoidal tumor. Most of these are benign growths.
  • Malignancies- over 20% cases with malignancies will develop hypercalcemia at some point in their disease condition. Secondary deposits of cancers of lung or the breast are also common causes. Production of osteoclastic factors by tumors as in case of multiple myeloma is another common cause.[4]
  • Endocrine diseases- Thyrotoxicosis and Addision's disease
  • Immobility over a long period of time 

2. GASTROINTESTINAL ABSORPTIVE HYPERCALCEMIA

  • "Milk alkali” syndrome- an increase in calcium intake
  • Sarcoidosis/ Paget's disease/ Tuberculosis
  • Excess of vitamin D - iatrogenic or self administered.

3. RENAL RESORPTIVE HYPERCALCEMIA

Epidemiology

Hypercalcemia is a common clinical occurrence which has a long duration and is mostly mild. Postmenopausal women above the age of 50 are at a higher risk, as primary hyperparathyroidism is the most common etiological factor. [5]
It occurs in 1 in 1000 population, mainly affecting elderly females. Many a times, most cases go unnoticed. Hypercalcemia tends to occur with advancing age, where hyperparathyroidism and malignancy are the main reasons.
In cases of malignancy, hypercalcemia is frequently encountered as an endocrine electrolyte disorder in hospitalized patients. The occurrence in children is unknown and rare; it is also thought to be a rare occurrence in young adults.

Sex distribution
Age distribution

Pathophysiology

The human skeleton stores 98% of total body calcium while the remaining 2% circulates through the body. Out of this 2%, half is bound to proteins such as albumin and globulin and the remaining is present in the free ionized form which has the physiological effects. Thus, measuring the free calcium level is more accurate. The level of circulating protein, mainly albumin, should also be taken into account for a correct measurement. The ionized calcium or the unbound calcium is physiologically important as it takes active part in cellular activities and neuromuscular functions. [6]
Corrected [CA] =Total [CA] + (0.8 x [4.5-albumin level])
An increase in bone resorption, increased gastrointestinal absorption or a reduced excretion of calcium by kidneys can cause hypercalcemia. Total serum calcium levels between 10.5 and 12 mg per dL are considered mild while levels above 14 mg per dL can be fatal and serious.
Generally when calcium levels fall, PTH [7] a hormone secreted by parathyroid glands increases calcium levels by stimulating bone resorption and accelerating tubular resorption of calcium. Calcitrol levels also increase thereby increasing calcium levels. As PTH increases calcium, it simultaneously causes an increased excretion of phosphate by the kidneys. Thus patients show low serum phosphate levels along with hypercalcemia. Along with this PTH also causes an increase in 1, 25 dihydroxy vitamin D synthesis further aggravating hypercalcemic state.
Calcium absorption from the gut is usually reduced. Impairment of glomerular filtration can also cause hypercalcemia.

The pathophysiology is varied and can be classified as three separate syndromes-

  1.  the hypercalcemia of malignancy caused by systemic mediators
  2. the hypercalcemia along with localized osteoclastic disease
  3. the hypercalcemia associated with myeloma.

Increased bone resorption is the characteristic feature in all the three syndromes. In malignancies, tumor cells as well host cells stimulate humoral mediators which cause an enhanced activity of osteoclasts. This leads to hypercalcemia when the rate of entry of calcium in the blood increases in comparison to its removal from blood. Therefore when GI and osteoclastic bone absorption increases the levels of calcium, beyond the capacity of kidneys to eliminate it, that is when calcium enters the extra cellular fluid compartment and renal excretion or bone mineralization get impaired. Hypercalcemia is always preceded by hypercalciuria. When the kidney is unable to excrete the excess calcium, the patient develops hypercalcemia. A hypercalcemia state interferes with the action of ADH hormone on the distal tubule causing a state of nephrogenic diabetes insipidus resulting in polyuria. With the nausea and vomiting, thirst mechanism may not be active thus dehydration may occur.

Prevention

There is no prevention for hypercalcemia other than early detection and treatment. An accurate diagnosis of the underlying cause will help to stabilize calcium levels faster. Any known history of hypercalcemia or hyperparathyroidism in the family should be mentioned to the physician for early screening and detection. Women above 50 should regularly check calcium levels if they show symptoms of hypercalcemia. Vitamin D and calcium supplements should be taken only under the guidance of a physician.

Summary

Hypercalcemia is a clinical condition characterized by elevated levels of calcium in the blood. It is much more common than hypocalcaemia and is frequently detected incidentally with multichannel chemical analyzers. The normal range of calcium is 9-10.5 mg/dl or 2.2-2.6mmol/L. Mild asymptotic hypercalcemia is mainly a laboratory finding and usually suggestive of some other disease which needs a careful work up and treatment. [1]
Calcium is a vital mineral of the body required for optimal functioning of the bones, muscles and nerves. The main regulators of calcium in the body are PTH, Vitamin D and calcitonin. Parathyroid hormone is released by parathyroid glands [2] which is the chief regulator of calcium in the body. Calcitonin is produced by specialized cells of the thyroid gland. Together these three hormones act on the kidneys, bones and GI tract to maintain levels of calcium in the blood stream. The simplest way to remember the presentation of hypercalcemia is by the phrase "moans, stones, groans and bones”. The intensity, duration and severity of this condition vary. The most common cause of hypercalcemia is hyperparathyroidism. Most cases of malignancies have hypercalcemia as an associated condition. Onset of hypercalcemia usually indicates a poor outlook for malignancies.
The options of treatment depend upon the severity and cause of hypercalcemia. Both medical and surgical modes of treatment are available. The outlook of this condition majorly depends upon the causation.

Patient Information

Hypercalcemia is a clinical condition where there are increased calcium levels in the blood. The normal levels of calcium in the body are 9-10.5mg/dL. Most times mild cases of hypercalcemia are not detected and go unnoticed. Calcium is an important mineral required by the body for smooth functioning of the bones, muscle, nerves and brain. Calcium is maintained in the body by three hormones which are PTH, Vitamin D and calcitonin. Any irregularity in these three causes calcium levels to fall or rise. The most common cause is the over activity of parathyroid glands which are four small glands situated near the thyroid gland which cause increase in PTH levels which thereby causes increased calcium levels. No obvious symptoms are seen, but slowly it can lead to major clinical conditions like tiredness, bony pains, alterations in blood pressure and bowel function. It is more common in menopausal women. A simple blood test can check blood calcium levels. A PTH level can also be checked for. Some scans maybe required incase of cancers or tumors. A consultation with your physician will help you control calcium levels. Treatment mainly involves lowering levels of calcium along with adequate hydration. Calcium and vitamin D supplements should always be taken under medical guidance.

References

Article

  1. Royer AM, Maclellan RA, Daniel Stanley J, Willingham TB, Heath Giles W. Hypercalcemia in the emergency department: a missed opportunity. Am Surg. Aug 2014;80(8):732-5.
  2. al Zahrani A, Levine MA. Primary hyperparathyroidism. Lancet. Apr 26 1997;349(9060):1233-8.
  3. Allerheiligen DA, Schoeber J, Houston RE. Hyperparathyroidism. Am Fam Physician. Apr 15 1998;57(8):1795-802, 1807-8.
  4. Mundy GR, Guise TA. Hypercalcemia of malignancy. Am J Med. Aug 1997;103(2):134-45.
  5. Luna-Cabrera F, Justicia-Rull EA, Caricol-Pérez MP, et al. Incidence of hypercalcemia, hypercalciuria and related factors in patients treated with recombinant human parathyroid hormone (1-84). Minerva Med. Apr 2012;103(2):103-10.
  6. Pearce SH. Calcium homeostasis and disorders of the calcium-sensing receptor. J R Coll Physicians Lond. Jan-Feb 1998;32(1):10-4.
  7. Strewler GJ. The physiology of parathyroid hormone-related protein. N Engl J Med. Jan 20 2000;342(3):177-85.
  8. Alsirafy SA, Sroor MY, Al-Shahri MZ. Hypercalcemia in advanced head and neck squamous cell carcinoma: prevalence and potential impact on palliative care. J Support Oncol. Sep-Oct 2009;7(5):154-7.
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Last updated: 2018-06-22 12:21