INTRODUCTION:

Endocrine glands are the type of glands that release hormones directly into the bloodstream. The thyroid gland is the largest endocrine gland in the human body and is considered to be the cornerstone of the complete endocrine system.¹ The shape of the gland is H or U split up into lobes connected with a median isthmus. The gland weighs about 25-30g and its length approximately ranges from 50-60mm.^2,4Thyroxine, Triiodothyronine, and calcitonin alter the number and activity ofthe mitochondrial respiratory chain components.^5,6 The thyroid gland secretes the hormone calcitonin which is implicated in the homeostasis of blood calcium levels.⁷ Thyroid hormones carry out multiple physiological functions including growth, development, metabolism, and bone and heart physiology.^8,10

Hormones are endocrinal secretions that are released by endocrine glands directly into the systemic circulation.¹¹ Over 50 different hormones existed in the human body. Different hormones are involved in basic metabolism processes.¹² Calcium and phosphorous metabolism are regulated by the majority of four main hormones. Among PTH, Vitamin D, FGF23, and Calcitonin.¹³ Calcitonin is a forsaken hormone. Research studies related to calcitonin in physiological and pathological are limited. Calcitonin exhibits a hypercalcemia effect produced due to multiple reasons that resulted from bone resorption or suppression of calcium release from bone. Utility of calcitonin as hypercalcemia effect used for the treatment of bone disorders such as osteoporosis, hypercalcemia, and Paget’s disease. Development of new formulation decline calcitonin usage.¹⁴

Structural Description:

In the human body, calcitonin is released from parafollicular cells (C -cells) present in the thyroid gland, and other vertebrates are released from the ultimo pharyngeal body. Chemically calcitonin also known as thyrocalcitonin is composed of 32 amino acids. It is a resultant product of biochemical reactions generated from the proteolysis of larger perpropeptides. Calcium exhibits antagonizing PTH and vitamin D3 to balance calcium and phosphorous level in human physiology. Calcitonin goes through interweaving which is resultant in a new 37 amino acid neuropeptide. This new combination of calcitonin-gene related is a potent vasodilator produced from neurons in both the central and peripheral nervous system^.15

Physiological Role:

Maintaining Calcium Homeostasis During Calcium Stress:

During the Gestation period, calcium homeostasis gets disturbed, as calcium is retained by the fetus in increasing amounts regardless of the mother’s calcium. In the case of a nursing mother, calcium is released in milk according to a concentration gradient, and the released calcium is maintained within the maternal skeleton. In nursing mothers long time, breastfeeding can reduce bone density. (Figure 1) Calcitonin seems to exhibit a shielding effect in preserving skeletal mineral content by preventing excessive osteoclast-mediated bone resorption that is stimulated by PTHrP. Research studies concluded the fact that pregnancy-associated osteoporosis is caused by a relative CT deficiency.¹⁶

Fig 1: Role of calcitonin during gestation and lactation period

Miscellaneous Effects:

Among the lesser-known effects of CT are certain interactions with other hormones that appear to occur at high doses and therefore do not appear to have practical or therapeutic implications. These effects include anti-stress, anti-ulcer, and possibly anti-inflammatory effects. Other rare effects of CT include decreased prostaglandin synthesis, in vitro inhibition of breast cancer cells, stimulation of plasminogen activators, and salivary gland amylase secretion. Adverse effects such as flushing and diarrhea in patients after multiple endocrine tumors, metastatic bone syndrome, and parenteral demonstration of CT may be the result of the excessive temporary release of CT into the circulation.¹⁷

Pharmacological Indications:

Anodynic action:

Different hypothetical mechanisms support the anodynic action of calcitonin. According to the initial theory, calcitonin decreases serotonin transporters, thus increasing the availability of serotonin receptors in the thalamus. This mechanism of action was observed in patients administering calcitonin, therefore beneficial in neuropathic pain and osteoporosis. Another hypothesis involved endorphin mediated mechanism. It was observed that calcitonin intake in migraine patients helps to release an increased amount of endorphin, adrenocortropic hormones, and corticosteroid hormones. Physiologically these hormones are released in response to pain and stress, thus relieving pain in the body. Preclinical studies exhibit dose-dependent anti-inflammatory effects.Clinical studies are mandatory to report the anti-inflammatory action of calcitonin.¹⁸

Hypo calcaemic effect:

In the human body, calcitonin maintains an excessive level of calcium in the systemic circulation. Synthetically prepared calcitonin is given to reduce vertebral fractures that develop in postmenopausal osteoporotic females. This hypocalcemic effect is developed due to various causes such as reduction of calcium release from bone or inhibition of bone resorption.Thus, calcitonin is a chief regulator of the bone resorption process, used in the treatment of osteoporosis, hypercalcemia, and Paget disease.⁴

Cardioprotective:

In various pathological conditions primarily in cardiovascular disease, CGRP produces the cardioprotective response. Preclinical and clinical studies favor the cardioprotective action of calcitonin. In human studies, CGRP acts as a cardioprotective agent in cardiac infarction by reducing afterload and developing inotropy.¹⁹

Calcitonin as Diagnostic Parameter:

1. Neurological Disorders: Researchers detect the increased level of calcitonin in systemic circulation and sputum evaluation. Neuralgia, Migraine, and rhinosinusitis are pathological conditions that resulted in raised calcitonin levels.

2. Oncological Disease: Scientists observed elevated calcitonin levels in different types of tumors (Pancreatic, Lung, Breast, and Insulinomas).

3. Additional Pathological Conditions: Chronic renal failure, Zollinger-Ellison syndrome, Pernicious Anaemia (Figure 3).²⁰

Fig 2: Pharmacological action of Calcitonin

Fig 3: Calcitonin as Diagnostic parameter

Calcitonin and Hypertension:

It was observed that patients with high renin activity result in hypertension. Laboratory assessment parameter indicates that calcitonin levels are high in hypertensive patients. The study was conducted on 51 patients with essential hypertension.²¹

Involvement of PTH and Calcitonin in the Regulation of Calcium and Phosphate Levels:

Physiologically calcium and phosphorous are in equilibrium due to the presence of calcitonin and parathyroid hormone. Ideally normal calcium level in the human body ranges from 8.6-10.3 mg/dl while phosphorous ranges from 2.8-4.5 mg/dl in adults.²² Parathyroid hormone acts by enhancing the release through the activation of the bone resorption process and calcium from renal calcium absorption.²³

Nicotine dependence, Alcoholism, and Calcitonin:

Calcitonin and PTH level are disturbed by alcohol and tobacco consumption. Research studies conducted on large populations confirm the positive relationship between nicotine dependence, alcoholism, and calcitonin.²⁴Additionally, some studies also support the statement that smoking during the gestation period also leads to increase calcitonin levels. Heavy metals such as cadmium &thiocyanate are the toxic components of tobacco smoke. Hematological evaluation of these heavy metals revealed high calcitonin levels.²⁵

Calcitonin and Smoking:

Clinical studies were conducted to generate a relationship between smoking and calcitonin. In humans, smoking of two high-nicotine-contentcigarette smoking elevates serum and urine levels of hormones. These recorded results show the presence of calcitonin does not appear in thyroidectomized patients but can appear in the lungs too.²⁶

Calcitonin and Physical activity:

A study on 30 people including exercise in their daily routine indicates high calcitonin. The mechanism behind raised calcitonin was increased aldosterone levels during exercise.²⁷

MATERIAL METHODS:

A literature review was conducted for the present study. The relevant data were collected from PubMedand google scholar.

RESULTS AND DISCUSSIONS:

The present study shows that calcitonin levels are not only raised in diagnosing C -cell hyperplasia and medullary thyroid cancer, but other conditions are responsible for increased calcitonin in the systemic circulation

CONCLUSION:

Calcitonin is considered anabandoned hormone. The importance of calcitonin is not well known. This review enlightens some of the emerging physiological and therapeutic roles of calcitonin.Despite its role in diagnosing c-cell hyperplasia and medullary thyroid cancer,its abnormal lab values are also observed in chronic renal failure, Zollinger-Ellison syndrome, and Pernicious Anaemia, migraine. In the succession rate of research studies, calcitonin is useful both as an analgesic agent and monoclonal antibody for the treatment of migraine.Further investigation is requisite for extracting more and more information regarding calcitonin.

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Received on 30.11.2022 Modified on 20.05.2023

Research J. Pharm. and Tech 2024; 17(4):1881-1884.

DOI: 10.52711/0974-360X.2024.00298