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What is the adjusted calcium value range considered normal?
What is the adjusted calcium value range considered normal?
Primary hyperparathyroidism is more common in males than females.
Primary hyperparathyroidism is more common in males than females.
False
What is the most common cause of hypercalcemia?
What is the most common cause of hypercalcemia?
Primary hyperparathyroidism
Hypercalcemia is defined as a calcium level greater than ______ mg/dl.
Hypercalcemia is defined as a calcium level greater than ______ mg/dl.
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Match the following conditions with their relevant cause or characteristic:
Match the following conditions with their relevant cause or characteristic:
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What is the first line treatment for hypercalcaemic crisis?
What is the first line treatment for hypercalcaemic crisis?
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Surgery has no role in the management of parathyroid adenoma.
Surgery has no role in the management of parathyroid adenoma.
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What is the primary indication for surgery in asymptomatic patients with parathyroid adenoma?
What is the primary indication for surgery in asymptomatic patients with parathyroid adenoma?
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The preferred IV bisphosphonate for treating hypercalcaemic crisis is __________.
The preferred IV bisphosphonate for treating hypercalcaemic crisis is __________.
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Match the following treatments with their corresponding details:
Match the following treatments with their corresponding details:
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What percentage of calcium is reabsorbed in the Thick Ascending Limb (TAL)?
What percentage of calcium is reabsorbed in the Thick Ascending Limb (TAL)?
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Hypocalcemia triggers the release of parathyroid hormone (PTH).
Hypocalcemia triggers the release of parathyroid hormone (PTH).
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What is the role of the Calcium Sensing Receptor (CaSR) in calcium regulation?
What is the role of the Calcium Sensing Receptor (CaSR) in calcium regulation?
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Approximately _____ mg of calcium is lost in urine.
Approximately _____ mg of calcium is lost in urine.
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Match the calcium reabsorption sites with their respective mechanisms and PTH dependence:
Match the calcium reabsorption sites with their respective mechanisms and PTH dependence:
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What is the primary outcome of a gain of function mutation of CaSR?
What is the primary outcome of a gain of function mutation of CaSR?
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Familial hypocalciuric hypercalcemia is an autosomal recessive disorder.
Familial hypocalciuric hypercalcemia is an autosomal recessive disorder.
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What is the half-life of calcitriol?
What is the half-life of calcitriol?
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In Bartter syndrome Type V, excessive CaSR activation leads to ________.
In Bartter syndrome Type V, excessive CaSR activation leads to ________.
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Match the conditions with their genetic inheritance:
Match the conditions with their genetic inheritance:
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What PTH level indicates a parathyroid-dependent cause of hypercalcemia?
What PTH level indicates a parathyroid-dependent cause of hypercalcemia?
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A Tc99 sestamibi scan is used to locate a parathyroid adenoma.
A Tc99 sestamibi scan is used to locate a parathyroid adenoma.
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What condition is most commonly associated with low intact PTH levels?
What condition is most commonly associated with low intact PTH levels?
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Hypervitaminosis D can lead to __________ levels of both 25(OH)D and 1,25(OH)D.
Hypervitaminosis D can lead to __________ levels of both 25(OH)D and 1,25(OH)D.
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Match the following parameters with their possible diagnosis:
Match the following parameters with their possible diagnosis:
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Which of the following is investigated when intact PTH levels are low?
Which of the following is investigated when intact PTH levels are low?
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Small cell carcinoma is the most common paraneoplastic tumor associated with hypercalcemia.
Small cell carcinoma is the most common paraneoplastic tumor associated with hypercalcemia.
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An increased serum phosphate level suggests a possible __________ adenoma.
An increased serum phosphate level suggests a possible __________ adenoma.
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Which symptom is most commonly associated with chronic hypercalcemia?
Which symptom is most commonly associated with chronic hypercalcemia?
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Constipation is a common symptom of chronic hypercalcemia.
Constipation is a common symptom of chronic hypercalcemia.
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What does a short QT interval on an ECG indicate in the context of hypercalcemia?
What does a short QT interval on an ECG indicate in the context of hypercalcemia?
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The mnemonic for remembering symptoms of hypercalcemia includes 'Painful', 'Renal', 'Abdominal', 'Psychotic', and '______.'
The mnemonic for remembering symptoms of hypercalcemia includes 'Painful', 'Renal', 'Abdominal', 'Psychotic', and '______.'
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Match the following symptoms with their appropriate clinical feature of hypercalcemia:
Match the following symptoms with their appropriate clinical feature of hypercalcemia:
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Which of the following conditions is most commonly associated with a decrease in serum calcium, an increase in serum phosphate, and a decrease in serum PTH?
Which of the following conditions is most commonly associated with a decrease in serum calcium, an increase in serum phosphate, and a decrease in serum PTH?
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DiGeorge syndrome is associated with a TBX1 gene mutation, which can lead to hypoparathyroidism.
DiGeorge syndrome is associated with a TBX1 gene mutation, which can lead to hypoparathyroidism.
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What mnemonic can help remember the characteristics associated with DiGeorge syndrome?
What mnemonic can help remember the characteristics associated with DiGeorge syndrome?
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In chronic kidney disease, serum calcium is typically ______ and serum phosphate is ______.
In chronic kidney disease, serum calcium is typically ______ and serum phosphate is ______.
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Match the following causes of hypocalcemia with their descriptions:
Match the following causes of hypocalcemia with their descriptions:
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What is the most common cause of malignancy associated hypercalcemia?
What is the most common cause of malignancy associated hypercalcemia?
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Jensen's disease is inherited in an autosomal dominant manner.
Jensen's disease is inherited in an autosomal dominant manner.
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What type of mutation is associated with the PTH Type 1 receptor in Jensen's disease?
What type of mutation is associated with the PTH Type 1 receptor in Jensen's disease?
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The primary defect in Familial Hypocalciuric Hypercalcemia (FHH) is the loss of function of the _________.
The primary defect in Familial Hypocalciuric Hypercalcemia (FHH) is the loss of function of the _________.
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Match the following conditions with their features:
Match the following conditions with their features:
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Which of the following symptoms is NOT associated with acute hypocalcemia?
Which of the following symptoms is NOT associated with acute hypocalcemia?
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Chvostek's sign has high sensitivity and specificity in diagnosing hypocalcemia.
Chvostek's sign has high sensitivity and specificity in diagnosing hypocalcemia.
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What is a common cardiac manifestation of prolonged QT interval in hypocalcemia?
What is a common cardiac manifestation of prolonged QT interval in hypocalcemia?
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In chronic hypocalcemia, symptoms may include _____ and dry skin.
In chronic hypocalcemia, symptoms may include _____ and dry skin.
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Match the hypocalcemia signs with their descriptions:
Match the hypocalcemia signs with their descriptions:
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What is the most common cause of primary hyperparathyroidism?
What is the most common cause of primary hyperparathyroidism?
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Secondary hyperparathyroidism is characterized by elevated levels of calcium.
Secondary hyperparathyroidism is characterized by elevated levels of calcium.
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What PTH level is indicative of tertiary hyperparathyroidism?
What PTH level is indicative of tertiary hyperparathyroidism?
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In primary hyperparathyroidism, phosphate levels are typically ______.
In primary hyperparathyroidism, phosphate levels are typically ______.
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Match the following radiological bone changes with their characteristics:
Match the following radiological bone changes with their characteristics:
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Study Notes
Hypercalcemia
- Adjusted Calcium Value: 8.6 - 10.3 mg/dl
- Hypercalcemia: > 10.5 mg/dl (initiate evaluation)
-
Parathyroid gland dependent (80%): Most common cause is primary hyperparathyroidism
-
Primary hyperparathyroidism: Most common cause overall
- More common in females
- Typically seen in the 6th decade
-
Types:
- Primary adenomas (85%): Inferior parathyroid
- Hyperplasia (multiple Type 1 > Type 2A)
- MEN: CDC73 (carcinoma)
- Sporadic
- Familial Hypocalciuric Hypercalcemia (FHH) AD
- Calcium sensing receptor (CaSR) loss of mutation
- Low 24 hr urine calcium
- Lithium therapy: Inhibits CaSR
- Tertiary hyperparathyroidism: In CKD (Chronic Kidney Disease)
-
Primary hyperparathyroidism: Most common cause overall
- PTH-related peptide dependent (PTH-rP): Squamous cell carcinoma: lung, head and neck
-
Vit-D Related (20%):
- Hypervitaminosis
- Tumor producing 1, α-hydroxylase: Lymphoma
-
Miscellaneous:
- Endocrine: Addison's disease, Pheochromocytoma, Thyrotoxicosis
- Milk alkali syndrome
- Thiazide induced
- Osteolytic hypercalcemia: Ca breast (most common), Ca lung, Multiple myeloma
- Sarcoidosis
- Acromegaly
Osteitis Fibrosa Cystica
- Bone reabsorption > Formation > Fracture
- Fibrous & cystic changes
Management of Parathyroid Adenoma
- Absolute treatment: Surgery (No role of medical management)
- Excision of single large gland is curative.
-
Indications of surgery
- Symptomatic: All patients
- Asymptomatic: < 50 years old, Renal failure, > 400 mg/day 24 hr urine Ca²⁺, Osteoporosis, S.Ca²⁺ > 1 mg/dl from baseline
Hypercalcemic Crisis
-
Treatment*
-
1st line*
-
Fluids: 300-400 ml/hr continuous
-
IV Lasix (not recommended)
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Calcitonin: 4 u/kg S/C BD
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IV bisphosphonate: Zolendronate: 4mg IV in 50 ml saline + 50 ml dextrose 5% (preferred), Pamidronate
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2nd line*
-
Steroid: Oral prednisolone. Used only in Osteolysis, Vit-D dependent cause
-
Denosumab
Excretion
- Approximately 200mg of calcium is lost in urine
- 4 mg/kg/24 hours of calcium loss may indicate hypercalciuria
-
4 mg/kg/24 hours of calcium loss is likely hypercalciuria (most common reason for stones)
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7 mg/24 hrs calcium loss may indicate hyperuricosuria
- 4 g/day sodium intake may lead to increased paracellular Ca entry
Fate of Calcium in Kidneys
| Site | Ca2+ Reabsorption | Mechanism | PTH Dependence |
|---|---|---|---|
| PCT | 65% | Paracellular Transport | Independent |
| TAL | 25% | Paracellular Transport | Dependent |
| DCT | 10% | Active Transport | Most Dependent |
Calcium Regulation Pathway
- Within seconds: Increase in ionized calcium leads to a response
- Within few days: Decrease in ionized calcium leads to PTH release
- CaSR (Calcium Sensing Receptor): Key regulator in calcium homeostasis, responding to both hypocalcemia and hypercalcemia
- Kidney (TAL): Regulates calcium reabsorption via CaSR, influencing hypercalciuria
- Hypocalcemia (immediate response): Triggers PTH release
- Hypercalciuria (delayed response): Results in reduced Ca2+ reabsorption
Laboratory Investigation for Hypercalcemia
-
High Intact PTH (iPTH) Level (> 50 pg/mL): Parathyroid-dependent
- Increased serum calcium (S.Ca²⁺)
- Decreased serum phosphate (S.Phosphate)
- Increased 24-hour urine calcium
- Investigation: Parathyroid adenoma (most common), Imaging: Tc99 sestamibi scan (10C) to locate the adenoma.
-
Low Intact PTH Level (< 50 pg/mL): Parathyroid-independent
- Vit D-related: Investigate 25(OH)D and 1,25(OH)2D levels
- Investigation: Look for tumors, hypervitaminosis D, lymphoma, acromegaly, sarcoidosis
-
Normal PTH: Suspect parathyroid-dependent causes
- Increased serum calcium (S.Ca²⁺)
- If PTH value is normal: serum calcium (S.Ca²⁺) is elevated
- If normal PTH level suspect paraneoplasm, especially Small cell carcinoma (m/c in lung)
- Investigation: CT/PET
- Paraneoplastic Tumor (m/c in Small Cell Lung Cancer (SCC)): Investigation: CT/PET scan
Table of Investigations
| Parameter | Abnormal Value | Possible Diagnosis | Investigation |
|---|---|---|---|
| 25(OH)D | ↑ | Hypervitaminosis D | Serum 25(OH)D/ 1,25(OH)2D |
| 1,25(OH)D | ↑ | Hypervitaminosis D | Serum 25(OH)D/1,25(OH)2D |
| PTH | ↑ or Normal | Parathyroid adenoma /parathyroid independent | Tc99m sestamibi scan, CT/PET/biopsy |
| Calcium | ↑ | Parathyroid adenoma/hypervitaminosis D/parathyroid indepedent | |
| Phosphate | ↓ | Parathyroid adenoma | Serum phosphate |
| 24-hr urine calcium | ↑ | Parathyroid adenoma | Urine collection |
Endocrinology
-
Half lives:
- PTH: 2-4 mins
- Calcitriol: 6-8 hours
- 25(OH)D: 2-3 weeks
- Used for blood level estimations.
Gain of function mutation of CaSR
- Bartter syndrome Type V.
- Autosomal dominant
- Pathway: Excessive CaSR activation ↑↑↑↑ Excretion → Hypocalcemia
Loss of function mutation of CaSR
- Seen in children.
- Familial hypocalciuric hypercalcemia (FHH).
- Autosomal Dominant disorder.
- Pathway: Failure of CaSR activation → No excretion → Complete reabsorption → Hypocalciuria + Hypercalcemia
Hypocalcemia
- S.Ca: 58.4 mg/dL
Presentation
-
Acute Hypocalcemia*
-
Neuromuscular irritability:
- Laryngeal spasm leading to death
- Arrhythmias with prolonged QT intervals and possibility of Torsades de pointes
- Central Nervous System (CNS) seizures (Generalized Tonic Clonic Seizures - GTCS)
-
Apparent symptoms: Tingling, Twitching, Fasciculations, Circumoral paresthesia, Tetany
-
Chronic Hypocalcemia*
-
Symptoms: Basal ganglia calcification, Benign intracranial hypertension (pseudo tumor cerebri), Cataracts, Dry skin
-
Latent Hypocalcemia*
-
Signs:
- Chvostek's Sign: Reduced sensitivity and specificity
- Trosseau's Sign: Inflate cuff to 20 mmHg over systolic blood pressure (SBP) → carpopedal spasm
-
Calcifications in chronic hypocalcemia*
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Arrhythmias: Prolonged QT interval greater than 12 small boxes, Prolonged QT + polymorphic ventricular tachycardia (VT) → Torsades de pointes
Investigations to Differentiate Primary, Secondary, and Tertiary Hyperparathyroidism
Table of Differentiating Factors
| Feature | Primary/1° | Secondary/2° | Tertiary/3° |
|---|---|---|---|
| Cause | Adenoma (most common), Hyperplasia (MEN 1/2A) | Seen in Chronic Kidney Disease (CKD) | Long-standing CKD |
| PTH Level | > 50 pg/ml | 500 - 1000 pg/ml | > 1000 pg/ml |
| Calcium | ↑ | ↓ | ↑ |
| Phosphate | ↓ | ↓ | ↑ |
Radiological Bone Changes
- 1.Diffuse Bone Resorption (most common): Subperiosteal reabsorption, most noticeable on the radial side of the proximal or middle phalanx of the index and middle finger
- 2.Rugger Jersey Spine: Intercortical bone resorption
- 3.Brown Tumor: A specific type of bone lesion
- 4.Salt and Pepper Skull: A characteristic radiological finding
- 5.Endosteal Scalloping: A specific type of bone lesion
- 6.Acral Osteolysis (distal end): Resorption in the distal ends of bones
Causes of Hypocalcemia
-
↓ S.Ca²⁺, ↑ S.PO₃⁻, ↓ S.PTH: Hypoparathyroidism, Post-surgical
-
m/c cause: Non-surgical
- Adults: Polyglandular autoimmune (PGA) type (aka APECED = Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy)
-
Children: Inherited diseases: DiGeorge syndrome
- TBX1 gene mutation
- Mnemonic: CATCH22: Cardiac abnormalities, Abnormal facies, Thymic hypoplasia
-
m/c cause: Non-surgical
- ↓ S.Ca²⁺, ↑ S.PO₃⁻ (N)/ ↑ S.PTH: Cleft palate, Hypocalcemia, 22q microdeletion
-
Cellular Stress:
- Tumor lysis
- Rhabdomyolysis
- Hemolysis
- Other causes: Sepsis, Pancreatitis, CKD (Chronic Kidney Disease) -> Secondary hyperparathyroidism (↓ S.Ca²⁺, ↑ S.PO₃⁻, ↑ S.PTH), AKI (Acute Kidney Injury) -> (↓ Calcium, ↑ PO4)
Clinical Features of Hypocalcemia
- m/c Asymptomatic
- Acute: Abdominal Pain, Vomiting
- Chronic: Fatigue (and m/c), Painful bones
- Mimics: Pancreatitis
- Constipation
- Neuropsychiatric: Drowsiness, Lethargy, Confusion, Disorientation
- Arrhythmia (Short QT interval on ECG)
- mnemonic: Painful: Bone, Renal: Stone, Abdominal: Groan, Psychotic: moans, Fatigue: Overtone
- Renal: Recurrent stone, Recurrent UTI, Myopathy, Band Keratopathy, Pseudoclubbing
- Neurogenic diabetes insipidus: Polyuria, Dehydration, Pre-renal AKI
- Chronic tubulointerstitial disease (CTD)
- Note:*
- In Hypercalcemia: Diarrhea & seizures not seen.
- In Hypocalcemia: On ECG long QT interval.
Malignancy Associated Hypercalcemia
- PTH-rP (m/c): Humoral hypercalcemia of malignancy, A/W SCC lung
- Lymphoma: 1 α hydroxylase
- Causes of Osteolysis -> Hypercalcemic crisis: Ca breast (m/c), Multiple myeloma, Ca lung
Paediatric Hypercalcemia
Jensen Disease
| Feature | X-linked | FHH |
|---|---|---|
| Inheritance | X-linked | AD |
| Defect | Activation mutation of PTH Type 1 receptor | Loss of function of CaSR |
| * Short stature | * Mild symptom | |
| * Dementia | * Fatigue | |
| * Disorientation | * Weakness | |
| * Abnormal facies | ||
| * Severe bone involvement |
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Description
This quiz covers key aspects of hypercalcemia, including causes, types, and related conditions. It focuses on primary hyperparathyroidism and its complications, offering insights into clinical evaluation and management strategies.
