Understanding Calcium Imbalance: Hypercalcemia and Hypocalcemia

An essential mineral, calcium is involved in many physiological functions, such as blood coagulation, hormone release, heart contractility, and neuromuscular communication. For cells to operate normally, extracellular calcium concentrations must be kept in a delicate balance and within the limited physiological range of 9–11 mg%.

This equilibrium is maintained by the complex interactions between parathyroid hormone (PTH), the active vitamin D metabolite calcitriol, and feedback processes involving the kidneys, intestines, bones, and parathyroid glands. The intricacies of hypercalcemia and hypocalcemia are examined in this blog, along with their causes, clinical signs, methods of diagnosis, and available treatments.

HYPERCALCEMIA

Hypercalcemia refers to elevated levels of calcium in the blood, disrupting the normal feedback mechanisms that regulate serum calcium. There are various etiologies for hypercalcemia, including excessive PTH production, malignancy-related hypercalcemia, and vitamin D intoxication.

Causes of Hypercalcemia

1. Excessive PTH production:
   • Primary Hyperparathyroidism
   • Parathyroid Adenoma
   • Parathyroid Hyperplasia
   • Parathyroid Carcinoma
   • Tertiary hyperparathyroidism (long-term stimulation of PTH secretion in renal insufficiency)
   • Ectopic PTH secretion (rare)
2. Hypercalcemia of malignancy:
   • Overproduction of PTH-related protein
   • Solid tumors: pheochromocytoma, lytic skeletal metastasis, carcinoma of the breast, and myeloma
   • Excessive 1,25(OH)2 D production in granulomatous diseases (sarcoidosis, TB, silicosis, lymphomas)
3. Other causes:
   • Increased bone resorption in hyperthyroidism and immobilization
   • Excessive calcium intake through TPN, milk-alkali syndrome
   • Endocrine diseases (Pheochromocytoma, VIPoma)
   • Medications: Thiazide diuretics, vitamin A supplements, antiestrogens

Familial Hypocalciuric Hypercalcemia (FHH)

The hallmark of FHH, an autosomal dominant disorder, is decreased extracellular calcium sensing as a result of gene abnormalities that impact calcium-sensing receptors.

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Clinical Features of Hypercalcemia

Hypercalcemic patients may exhibit systemic symptoms such as pain in the right upper quadrant, jaundice, weight loss, and abdominal mass. It is possible to experience neuropsychiatric symptoms such altered personality and trouble concentrating. The degree of hypercalcemia is correlated with the severity of symptoms.

Diagnostic Approach

PTH levels, albumin concentration, and serum calcium levels are measured as part of the diagnostic examination of hypercalcemia. Finding the root cause can be aided by imaging studies like CECT scans and ultrasonography. The eighth AJCC TNM classification aids in the staging of gallbladder cancer.

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Treatment of Hypercalcemia

The course of treatment differs according on the severity of hypercalcemia. While considerable symptomatic hypercalcemia necessitates therapeutic therapy, mild asymptomatic instances may not require immediate care. Treatment possibilities include volume expansion, calcitonin, bisphosphonates, and, in cases where response is refractory, gallium nitrate. Palliation is the primary treatment for gallbladder cancer stage IVb. 
When treating high-risk lesions including R1 resection, positive lymph node involvement, and T4 tumors, adjuvant therapy—which includes gemcitabine and cisplatin—is taken into consideration.

Survival and Prognosis

Survival in carcinoma of the gallbladder depends on factors such as tumor stage, node involvement, histological differentiation, CBD involvement, and resection margins. The 5-year survival rates vary from 60% for T2 lesions to less than 20% for T3 lesions and are even lower for T4 lesions.

Conclusion

Hypercalcemia and carcinoma of the gallbladder are complex medical conditions that require a thorough understanding of their causes, clinical manifestations, and treatment options. A multidisciplinary approach involving medical, surgical, and palliative interventions is crucial for managing these conditions effectively. Regular monitoring and early intervention play key roles in improving patient outcomes.

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HYPOCALCEMIA

The unusually low blood levels of calcium known as hypocalcemia provide serious obstacles to the regular operation of several physiological functions. The complexities of hypocalcemia are examined in this blog, which also provides information on its causes, clinical signs, methods of diagnosis, and available treatments.

Etiology of Hypocalcemia

Hypocalcemia can be broadly categorized into two types based on parathyroid hormone (PTH) levels:

1. Low Serum PTH (Hypoparathyroidism):
   • Primary Hypoparathyroidism:
     • Damage to all four parathyroid glands during thyroid surgery.
     • Autoimmune endocrinopathies.
     • Infiltrative diseases like sarcoidosis.
   • Impaired PTH Secretion:
     • Surgical gland destruction or radiation.
     • Infiltration by metastasis.
     • Autoimmune disorders.
     • Reduced PTH function due to hypomagnesemia.
     • Autosomal dominant hypocalcemia.
2. High Serum PTH (Secondary Hyperparathyroidism):
   • Vitamin D Deficiency or Impaired Production:
     • Poor intake or absorption.
     • Renal insufficiency leading to impaired vitamin D production.
     • Vitamin D resistance conditions like pseudohypoparathyroidism.
   • Drugs:
     • Calcium chelators.
     • Bisphosphonates.
     • Drugs inhibiting bone resorption.
   • Miscellaneous Causes:
     • Acute pancreatitis.
     • Acute rhabdomyolysis.

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Clinical Manifestations of Hypocalcemia

The symptoms of hypocalcemia can vary in severity. Asymptomatic cases may go unnoticed, while moderate to severe hypocalcemia can present with:

• Paraesthesia, particularly in the fingers, toes, and circumoral region.
• Chvostek's sign: Tapping facial nerves causes twitching of the circumoral muscles.
• Trousseau's sign: Carpal spasm induced by inflating a blood pressure cuff.
• Seizures, carpopedal spasms, bronchospasm, and laryngospasm in severe cases.
• Increased QT interval on ECG.

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Diagnostic Approach of Hypocalcemia

To accurately diagnose hypocalcemia, a thorough evaluation that takes into account serum calcium, albumin, phosphorus, and magnesium levels is necessary. The distinction between secondary hyperparathyroidism and hypoparathyroidism must be made based on PTH values.

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Treatment Strategies of Hypocalcemia

Treatment for hypocalcemia is based on the degree, speed of onset, and coexisting problems. Intravenous calcium gluconate is the first line of treatment for acute, symptomatic hypocalcemia. If the hypocalcemia persists, intravenous infusion is then used. Vitamin D and calcium supplements are necessary for chronic hypocalcemia brought on by hypoparathyroidism. PTH (1-84) has emerged as a potentially effective treatment for hypoparathyroidism that is refractory.

Conclusion

Due to the complex nature of hypocalcemia and its range of etiologies, diagnosis and treatment must be approached with caution. In order to properly manage hypocalcemia, coordination between healthcare experts from different specializations is essential. Restoring calcium levels to the low-normal range is the aim of treatment in order to prevent problems brought on by both hypercalcemia and hypocalcemia. Patients with hypocalcemia benefit from individualized therapy, patient education, and routine monitoring.

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Hope you found this blog helpful for your NEET SS Endocrinology Preparation. For more informative and interesting posts like these, keep reading PrepLadder’s blogs.