INCREASED ENZYMATIC ACTIVITY OF THYROID PEROXIDASE-TREATMENT FOR CONGENITAL HYPOTHYROIDISM

INCREASED ENZYMATIC ACTIVITY OF THYROID PEROXIDASE-TREATMENT FOR CONGENITAL HYPOTHYROIDISM

P. J. Sujitha ¹ and S. Arunkumar ^{* 2}

Department of Pharmacology ¹, Vinayaka Mission College of Pharmacy, Salem - 636008, Tamil Nadu, India.

Department of Pharmacy Practice ², J.K.K. Nattraja College of Pharmacy, Kumarapalayam - 638183, Tamil Nadu, India.

ABSTRACT: Congenital Hypothyroidism may be defined as a heterogeneous group of disorders characterized by goiter or cretinism due to an absolute or relative deficit of the enzyme Thyroid Peroxidase (TPO), and it is action. Chronic hypothyroidism also leads to goiter and cretinism associated with end gland damage, dysfunction, cancer, and failure, including the retina, kidney, nervous system, heart, and vascular tissue damage. The screening for Congenital Hypothyroidism (CH) may either be in the form of a thyroid function test or via thyroid peroxidase antibodies test, as recently recommended by the Thyroid Federation Association (TFA). Unto now, the treatment of goiter and cretinism is levothyroxine supplement and gland surgery removal. This review will establish the effectiveness of the enzymatic drug (TPO) and its indication for the treatment of PCH when compared to other therapies. This review also highlights the enzyme thyroid peroxidase (TPO) role and current treatment strategies on Congenital Hypothyroidism (CH).

Congenital Hypothyroidism, Thyroid Peroxidase, Genetics, Thyroid peroxidase antibodies test, Gene and stem cell therapy

INTRODUCTION: The thyroid gland is an endocrine gland in the neck, which consists of two lobes connected by an isthmus. The thyroid gland secretes three hormones, thyroxine (T4), tri-iodothyronine (T3), and calcitonin ¹. The hormones thyroxine has important functions related to energy metabolism, control of body temperature, bone development, and maturation of the CNS, among other metabolic processes throughout the body. Thyroid diseases are arguably among the common endocrine disorder worldwide.

Common causes of hypothyroidism in children were thyroid Dysgenesis, Dyshormonogenesis, and Thyroiditis ². Congenital hypothyroidism is defined as mild iodine deficiency during pregnancy which may affect the neurodevelopment of the offspring, and it occurs due to deficiency of TPO or another factor including concomitant drug therapy such as corticosteroids ³.

India to no exception, according to the projections from various studies on the thyroid. Studies from Mumbai have suggested that congenital hypothyroidism is common in India, the disease occurring in 1 out of 2640 neonates when compared with the worldwide average value of 1 in 3800 subjects. In childhood, too, hypothyroidism can occur; in the clinical-based study also found that, out of 800 children with thyroid disease, 79% had hypothyroidism ⁴.

This article makes an attempt to revisit the importance of recent advances in treating Congenital Hypothyroidism.

Factor Affecting Thyroid Peroxidase:

The Risk Factor, Sign and Symptom of Congenital Hypothyroidism: The Risk Factor of Congenital Hypothyroidism include gender (Female are more prone to CH than Male) ⁵, anti-thyroid cancer treatment, manic depression, thyroid surgery, elderly generation, autoimmune disorders like diabetes or rheumatoid arthritis. Sign and symptoms of Congenital Hypothyroidism are experience weakness, sleepiness, slowness of speech, constipation, weight gain, edema of larynx, hearing loss, dry skin and coarse hair, puffy, depression, dysarthria, cold intolerance ^{6, 7, 8, 9}.

Complication of Primary Congenital Hypo-thyroidism are myxedema coma, diabetes, left ventricle hypertrophy, acute heart failure, hypositis, retroperitoneal fibrosis, pituitary hyperplasia, postdate delivery, macrosomia, bowel syndrome, supraseller chordoid glioma ^{10, 11, 12, 13, 14, 15}.

Dietary Factors: The factors affecting thyroid Peroxidase include Myrcia uniflora flavonoids, aqueous extract of kalanchoe brasilensis, usage of leucomalachite green products likes dyes ^{16, 17, 18}. Also anti-thyroid, cough medicine, sulfonamides, lithium, phenylbutazone, soybeans, millet, cassava, cabbage, root vegetables, flower vegetables, leafy vegetables, fruity vegetables, legumes, seafood, phenolic contaminates like chocolate, cookies, cakes, bonbons, salami, canned meat, sausages, eggs, bacon, cedevita (powder based vitamin juice), fruits juices, refreshing non-alcoholic drink bran bread, white bread full-fat cheese, cottage cheese, butter ^{19, 20, 21}. As well hard cheese, sour cream venison, animal fats, lamb, pork mushrooms, canned and pickled vegetables, potato, muesli dried fruits nuts, hard liquor, vegetables juices, powder, soups, tea, olive oil, milk, coffee, yoghurt, fresh fruits, chicken, turkey, beef, veal macaroni or rice, jam, vegan diet, and marmalade fruit compote plant oil, TPO is inhibited by the thioamide drugs, such as propylthiouracil and methimazole ^{22, 23, 24, 25}. In diagnostic immunohistochemistry, the expression of TPO is lost in papillary thyroid carcinoma ²⁶. Initially, dietary factors are increase secretion TPO, long-term intake causes decrease TPO secretion.

Current Therapy of Primary Congenital Hypothyrodism:

Levothyroxine: Levothyroxine is used to treat an underactive thyroid gland by it replaces low thyroid hormone level produced by your thyroid gland to help to maintain normal body homeostasis. Initial dosing ranging from 50 mcg/day in case of primary congenital hypothyroidism ²⁷. It is a prolonged therapy to maintain the body thyroxine level. Due to long-term use, they have common side effects like nervousness, insomnia, pyrexia, convulsions, acute psychosis, thyroid storm, tachycardia, arrhythmia ²⁸. I also have some drug interactions like iron, calcium, proton pump inhibitors like omeprazole, statins, and oestrogen ²⁹.

Removal Gland Surgery: Gland Removal Surgery helps to avoid complications like pain and to bleed in the respiratory tract and disturb body homeostasis ^{30, 31, 32}. This surgery has several complications like hemorrhage, respiratory obstruction like hematoma, bilateral recurrent nerve palsy, laryngeal edema, leukocytosis, tachycardia seroma, recurrent laryngeal nerve injury, thyroid storm, destruct the parathyroid gland, recurrent thyrotoxiocosis, hypertrophic SCAR/KELOID, rarely pneumothorax ^{33, 34, 35, 36, 37}.

Genetic: Congenital Hypothyroidism involves autosomal recessive/dominant genes characterized by the inability to utilize iodine in thyroid. Biallelic non–functional TPO mutation produces iodine organification defect; monoallelic mutation carrier will have normal thyroid function. The coordination between clinical phenotype and TPO genotype is mentioned in Table 1 ^{38, 39, 40, 41}.

TABLE 1: THE CO-ORDINATION BETWEEN CLINICAL PHENOTYPE AND TPO GENOTYPE

Recent Development in Congenital Hypo-thyroidism Therapy:

Gene Therapy: The Potential to extract functional thyroid follicular cells from the principle, recombinant technology. A Full-length cDNA clone for human thyroid peroxidase(TPO), which was inoculated into the mammalian cell as vector pECE was stably transfected into Chinese hamster ovary(CHO) cells. These clones assayed by human TPO mRNA, TPO protein, and TPO enzyme activity was seen, then it is further moved to culture ⁴². In this technique have several advantages like avoiding surgery complications as mention above and also avoid ADR caused by levothyroxine [it is permanent therapy for treating hypothyroidism] ⁴³. It also indicated dyslipidemia, toxic adenoma, thyroiditis, and some non-thyroidal illness, like some autoimmune diseases ^{44, 45, 46}.

Stem Cell Therapy: The Potential to extract functional thyroid follicular cells from embryonic stem cells (ESC’s) or induced pluripotent stem cells (iPSC’s) would have potentially directed for congenital or post-surgical hypothyroidism patients. The thyroid follicular cells were developed by the creation of two models that have allowed for the save of hypothyroid mouse recipients through the transplantation of thyroid follicular cells derived from mouse ESC’s. It is a preferred alternative to long-term pharmacologic therapy. Indeed, regenerative therapy would provide physiologic replacement of both T4 and T3 without reliance on an external source ^{47, 48}.

CONCLUSION: It is a major threat to over global. Unto now, the most effective method to treat this disease is levothyroxine supplement and gland surgery removal. Thus, it is meaningful to establish an effective and economical protocol for the enzyme thyroid peroxidase production, which helps in congenital hypothyroidism. The development of regenerative therapy based on stem cell technology helps to the development of Enzymatic drugs.

Our review concludes that an increase in the production of enzyme thyroid peroxidase by using the recent technology will be a solution for Congenital Hypothyroidism.

ACKNOWLEDGEMENT: I would like to thank the management and Principal of JKK Nattraja College of Pharmacy, Kumarpalayam, College, for providing all the facilities required to carry out my work.

CONFLICTS OF INTEREST: All authors declare no conflicts of interest.

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    How to cite this article:

    Sujitha PJ and Arunkumar S: Increased enzymatic activity of thyroid peroxidase-treatment for congenital hypothyroidism. Int J Pharm Sci & Res 2021; 12(6): 3316-19. doi: 10.13040/IJPSR.0975-8232.12(6).3316-19.

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