Endocrine - Thyroid Development

Introduction

The boundary endoderm in the floor region forms a pocket (marked by the foramen cecum) that separates from the surface and forms the thyroid. Cells originate on the surface of the floor and descend into mesoderm above aortic sac and into the hypopharyngeal eminence as "cords". These cells continue to descend until they reach their final destination in the neck adjacent to the thyroid cartilage.

This pathway forms a temporary duct (thyroglossal duct). There are abnormalities of incomplete or excessive descent of these thyroid precursor cells. The thyroid is one of the earliest endocrine organs to differentiate and has an important hormonal role in embryonic development. The early bundle of cells then forms the thyroid by first dividing to form 2 lobes separated by a narrow connecting isthmus.

| Lecture - Head Development | original page

• Functions from wk10, required for neural development, stimulates metabolism (protein, carbohydrate, lipid), reduced/absence = cretinism (see abnormalities)

Hormones - (amino acid derivatives) Thyroxine (T4), Triiodothyronine (T3)

Reading

• Human Embryology (2nd ed.) Larson
• The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Ch10: p230-233, Ch12: p280-282, Ch13: p319-347
• Before We Are Born (5th ed.) Moore and Persaud
• Essentials of Human Embryology Larson
• Human Embryology Fitzgerald and Fitzgerald Ch24: p166-167

Development Overview

Stage 13 and Stage 22 thyroid development

foramen caecum

• thyroid median endodermal thickening in the floor of pharynx, outpouch – thyroid diverticulum
• tongue grows, cells descend in neck
• thyroglossal duct - proximal end at the foramen cecum of tongue thyroglossal duct
• thyroid diverticulum - hollow then solid, right and left lobes, central isthmus

Thyroid Timeline

• 24 days - thyroid median endodermal thickening in the floor of pharynx, outpouch – thyroid diverticulum
• Week 11 - colloid appearance in thyroid follicles, iodine and thyroid hormone (TH) synthesis

growth factors (insulin-like, epidermal) stimulates follicular growth

Fetal Thyroid Hormone

• Initial secreted biologically inactivated by modification, late fetal secretion develops brown fat
• Iodine deficiency- during this period, leads to neurological defects (cretinism)
• Birth - TSH levels increase, thyroxine (T3) and T4 levels increase to 24 h, then 5-7 days postnatal decline to normal levels

Thyroid Hormone

Thyroid hormone is synthesized in the thyroid gland by the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin.

Thyroxine (T4) - (Mr 777) majority of thyroid hormone derived from the thyroid gland. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood.

Triiodothyronine (T3) - synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4), though T3 is mainly used by tissues. Derived mainly from peripheral monodeiodination of T4 (at the 5' position of the outer ring of the iodothyronine nucleus).

(Data: PubChem)

Links: PubChem - T4 | PubChem - T3 |

Maternal Thyroid

Maternal thyroid related changes during pregnancy:

• stimulation of maternal thyroid gland by elevated levels of human chorionic gonadotropin (hCG)
• occurs mainly near end of first trimester associated with a transient lowering in serum TSH
• increase in serum thyroxine-binding globulin levels
• small decrease in free hormone concentrations (in iodine-sufficient conditions) significantly amplified in iodine restriction or overt iodine deficiency
• trend toward a slight increase in basal thyrotropin (TSH) values between first trimester and term
• modifications of the peripheral metabolism of maternal thyroid hormones

Abnormalities

Congenital hypothyroidism - approximately 1 in 3000 births, associated with neurological abnormalities.

Lingual thyroid gland - failure of thyroid descent.

Thyroglossal cyst - persistance of thyroglossal duct.

Thyroglossal fistula - partial degeneration of the thyroglossal duct.

Abnormal development of the thyroid - incomplete or excessive descent.

Pyramidal lobe - from isthmus (50% of people) attached to hyoid bone distal end of thryoglossal duct.

Childhood hypothyroidism delays ossification and bone mineralization.

Congenital Hypothyroidism

This abnormality can occur through either dysgenesis or agenesis of the thyroid gland development or abnormal thyroid hormone production.

American Academy of Pediatrics, Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS; Public Health Committee, Lawson Wilkins Pediatric Endocrine Society, Foley T, Kaplowitz PB, Kaye CI, Sundararajan S, Varma SK.Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006 Jun;117(6):2290-303. Review. PMID: 16740880

"Unrecognized congenital hypothyroidism leads to mental retardation. Newborn screening and thyroid therapy started within 2 weeks of age can normalize cognitive development. The primary thyroid-stimulating hormone screening has become standard in many parts of the world. However, newborn thyroid screening is not yet universal in some countries. Initial dosage of 10 to 15 microg/kg levothyroxine is recommended. The goals of thyroid hormone therapy should be to maintain frequent evaluations of total thyroxine or free thyroxine in the upper half of the reference range during the first 3 years of life and to normalize the serum thyroid-stimulating hormone concentration to ensure optimal thyroid hormone dosage and compliance. Improvements in screening and therapy have led to improved developmental outcomes in adults with congenital hypothyroidism who are now in their 20s and 30s. Thyroid hormone regimens used today are more aggressive in targeting early correction of thyroid-stimulating hormone than were those used 20 or even 10 years ago. Thus, newborn infants with congenital hypothyroidism today may have an even better intellectual and neurologic prognosis."

Iodine Deficiency

Iodine deficiency disorder (IDD) is the single most common cause of preventable mental retardation and brain damage in the world (More? Abnormal Development - Iodine Deficiency). It is required for synthesis of thyroid hormone, which in turn regulates aspects of neural development.

Worldwide:

1.6 billion people are at risk IDD affects 50 million children 100,000 cretins are born every year It causes goiters and decreases the production of hormones vital to growth and development. Children with IDD can grow up stunted, apathetic, mentally retarded and incapable of normal movement, speech or hearing. IDD in pregnant women cause miscarriage, stillbirth and mentally retarded children.

A teaspoon of iodine is all a person requires in a lifetime, but because iodine cannot be stored for long periods by the body, tiny amounts are needed regularly. In areas of endemic iodine deficiency, where soil and therefore crops and grazing animals do not provide sufficient dietary iodine to the populace, food fortification and supplementation have proven highly successful and sustainable interventions.

Iodized salt programs and iodized oil supplements are the most common tools in the fight against IDD.

(Data: ICCIDD)

Prolonged intake of large amounts (excess) of iodide can increase the incidence of goiter and/or hypothyroidism in humans. African Congo appears to be the only country that appears to have a dietary excess.

Maternal Abnormalities

File:10.1371 journal.pmed.0020370.g002-M.jpg

(A) Normal (B) Graves disease: diffuse increased uptake in both thyroid lobes. (C) Toxic multinodular goiter (TMNG): ‚Äúhot‚Äù and ‚Äúcold‚Äù areas of uneven uptake. (D) Toxic adenoma: increased uptake in a single nodule with suppression of the surrounding thyroid. (E) Thyroiditis: decreased or absent uptake. Image: Perros P. Thyrotoxicosis and pregnancy. PLoS Med. 2005 Dec;2(12):e370. Maternal Graves Disease - "The dose of anti-thyroid drug usually needs to be decreased during pregnancy, and often Graves disease remits completely and the medication can be withdrawn. This is probably due to the overall immunosuppressive effect of pregnancy." (Perros P. Thyrotoxicosis and pregnancy. PLoS Med. 2005 Dec;2(12):e370.) Graves' disease in mothers can cause thyrotoxic fetus - may have increased fetal motility and develop a range of abnormalities including: goitre, tachycardia, heart failure associated hydrops, growth retardation, craniosynostosis and accelerated bone maturation. Maternal Hashimoto's Thyroiditis (common autoimmune thyroid disease) usually no consequences on fetal thyroid, even if antibodies (anti-TPO and anti-Tg) found in the newborn due to transplacental passage. maternal hypothyroxinemia Links: NIH Genes & Disease - Chapter 41 - Endocrine | EPA (USA) - Radiation Technetium References Reviews Articles Search PubMed Search April 2010 Endocrine Development - All (14277) Review (4620) Free Full Text (3140) Search Pubmed: thyroid development Additional Images Adult Histology Thyroid (low power) Thyroid (high power) Terms Glossary Links Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link Cite this page: Hill, M.A. (2024, June 3) Embryology Endocrine - Thyroid Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Thyroid_Development What Links Here? © Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G