Introduction:
The parathyroid hormone produced by the parathyroid gland helps maintain the proper balance of calcium in the bloodstream and tissues that rely on calcium for appropriate functioning, which is essential for nerve and muscle functioning and bone health. Parathyroid hormone (PTH) secretion is based on the serum calcium level, and an excessive amount of parathyroid hormone can lead to imbalances in the functional physiological state of calcium metabolism.
What is Hyperparathyroidism?
It is an endocrine disorder with an excessive circulating parathyroid hormone. Excess PTH stimulates osteoclasts to mobilize calcium from the skeleton, leading to hypercalcemia (increased calcium level of the blood) and PTH-increased renal tubular re-absorption of calcium.
The bone and the kidney are the target organs of the parathyroid hormone, which mediates the osteoclast to resorb bone actively, and elevation of serum calcium level as the bone is resorbed, calcium is released in the extracellular fluid, and the serum calcium level is raised.
The parathyroid hormone acts on the epithelium of kidney tubules, causing diuresis of phosphorus and reducing serum phosphorus levels. It induces an increase in calcium reabsorption from the glomerular filtrate. The parathyroid hormone may also increase calcium absorption from the intestine, but this is not established. Therefore, in a healthy person, injection of the parathyroid hormone causes the following:
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Induce an elevated plasma calcium level.
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A decreased plasma phosphorus level.
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An increased alkaline phosphatase level.
What Are the Types of Hyperparathyroidism?
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Primary:
The autonomous secretion of parathyroid hormone (PTH) by hyperplasia, benign and malignant tumors of one or more of the four parathyroid glands that release the PTH.
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Secondary:
The state of a compensatory increase in output of PTH in response to hypocalcemia. The underlying hypocalcemia may result from inadequate dietary intake, poor absorption of vitamin D, or low vitamin D metabolism in the liver or kidney. It affects the restoration of serum calcium levels at the expense of calcium loss in bone.
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Tertiary:
The parathyroid tumor after long-standing secondary hyperparathyroidism increases the parathyroid level causing increased bone resorption and resultant hypercalcemia.
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Ectopic:
Ectopic hyperparathyroidism is caused due to excessive parathyroid hormone synthesized in a patient with a malignant disease.
What are the Clinical Features of Neonatal Severe Hyperparathyroidism?
Neonatal severe hyperparathyroidism (NSHPT) is an autosomal recessive condition due to a homozygous mutation of the calcium-sensing receptor (CaSR). The calcium-raised state leads to parathormone (PTH) secretion and renal absorption of calcium and is considered a rare cause of neonatal hypercalcemia and can be life-threatening. Hence, newborns affected with this condition present with extremely high PTH levels and severe hypercalcemia with a wide range of manifestations. The most common presentation of hyperparathyroidism is asymptomatic hypercalcemia of more than 12 milligrams/decilitre (mg/dL).
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Renal stones or calculi, resorption of bone, and duodenal ulcers.
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Psychological problems like emotional instability.
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Gastrointestinal difficulties like anorexia, nausea, vomiting, and cramp pain.
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Bone tenderness, pathological fractures, and bone deformities.
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Muscle weakness, fatigue, weight loss, insomnia, headache, polydipsia, and polyuria.
What are the Investigation Criteria for Hyperparathyroidism?
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Blood Picture:
To rule out calcium, phosphorus, and alkaline phosphatase serum level. The serum calcium level is raised, the serum phosphorus level is decreased, and the serum alkaline phosphatase level is elevated in primary hyperparathyroidism. In the case of secondary hyperparathyroidism, the serum calcium level is decreased, whereas the serum phosphorus and alkaline phosphatase levels are elevated.
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Radiological Method:
To rule out the pathology or abnormality of the parathyroid gland.
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Laboratory diagnosis:
Biopsy shows osteoclastic resorption of the trabeculae of the spongiosa and along the blood vessels in the Haversian system of the cortex (many tubes around narrow channels which surround blood vessels and nerve fibers in the bone). Fibrosis, especially in the marrow spaces, is marked. Radioisotope studies demonstrate an increase in circulating hormones.
What is the Treatment Plan for Neonatal Severe Hyperparathyroidism?
Maintenance of serum calcium within a secure range is the primary objective of treatment via
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Hydration.
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Forced diuresis.
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Bisphosphonate therapy.
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Parathyroidectomy.
Pharmaceutical Approach:
Calcitonin:
Calcitonin reduces serum calcium by interfering with osteoclastic activity, which can decline serum calcium levels by 1 to 2 mg/dL within a few hours. A dosage of 4 to 8 IU / kg subcutaneously every 12 hours of calcitonin is safe. Calcitonin is useful in treating cancer-associated hypercalcemia.
Bisphosphonates:
The drug works by inhibiting osteoclasts (bone-destroying cells) and is the drug of choice for cancer-associated hypercalcemia. Zoledronate can be delivered as a one-time dose of 4 to 8 mg intravenously IV and effectively declines serum calcium for an average of more than 40 days. Pamidronate is also a beneficial drug for cancer-associated hypercalcemia as a one-time dose of 30 to 90 mg intravenously IV, repeated only after seven days. It lowers serum calcium for less than two weeks.
Cinacalcet:
The drug belongs to the calcimimetics class. It functions by signaling the body to produce less parathyroid to prevent raising the calcium level. In the case of severe neonatal hyperparathyroidism, 6 mg orally (2 mg/kg per day) should be started at four months of age daily, which can cause a decrease in calcium level from 12.5 to 11.9 mg/dl over 18 h. Alkaline phosphatase decreased slowly and normalized after 15 weeks of Cinacalcet therapy.
Surgery:
In most cases, hyperplastic tissue should be removed surgically and followed by vitamin D supplements to prevent skeletal demineralization. The procedure starts with mobilizing the sternocleidomastoid on either side. Parathyroids are recognized as pink structures with no surrounding fat, unlike adults, which are more yellow with surrounding fat. Some of the four parathyroid glands are enlarged, others being minimally enlarged owing to hyperplasia. All four parathyroids with the thymus are isolated, carefully preserving both sides' recurrent laryngeal nerves (RLNs). The thymus is outlined till the innominate vein is ligated, and withdrawal has confirmed with a postoperative fall in parathormone to negligible levels, proving the completion of surgery. Further histopathological confirmation of parathyroids can be done.
Conclusion:
Parathyroid hormones are released to balance the calcium level in the bloodstream. The hypercalcemic states caused by increased circulating parathyroid hormone in newborns can lead to a fatal outcome. Proper diagnosis and treatment can help retain mineral elements' normal physiological and metabolic cycle.
