Thyroid Physiology And Diagnostic Evaluation Of Patients With Thyroid Disorders

Phylogeny, Embryology, and Ontogeny, 327 Anatomy and Histology, 329 Iodine and the Synthesis and Secretion of Thyroid Hormones, 330 Thyroid Hormones in Peripheral Tissues, 333 Regulation of Thyroid Function, 341 Physical Evaluation of the Thyroid Gland, 348 Laboratory Assessment of Thyroid Status, 349 Quantitation of Serum Thyroid Hormone Concentrations, 350

CHAPTER 11 CHAPTER
ThyroidPhysiology and Diagnostic Evaluation of Patients with Thyroid Disorders
DOMENICO SALVATORE • TERRY F. DAVIES • MARTIN-JEAN SCHLUMBERGER • IAN D. HAY • P. REED LARSEN
Dysfunction and anatomic abnormalities of the thyroid are among the most common diseases of the endocrine glands. This chapter provides the physiologic and biochemical background and describes the various tests for evaluating patientswith suspected thyroid disease based on the patho­ physiology of these conditions. kingdoms. However, the anatomy of the thyroid gland differs considerably among the vertebrate classes. Mono­ iodotyrosine (3′­monoiodo­L­tyrosine [MIT]) and diiodoty­ rosine (3,5­diiodo­L­tyrosine [DIT]) are present in a variety of invertebrate species, including mollusks, crustaceans, coelenterates, annelids,insects, and certain marine algae. However, no recognizable thyroid tissue is present in these lower forms. Thyroid tissue is confined to vertebrates, and is present in all vertebrates. A close link to the thyroid of higher vertebrates is evident in the ammocoete, the larval form of the lamprey, where the ventral part of the pharynx is the origin of a structure present only during larval life, theendostyle. The epithelium of the endostyle is capable of carrying out iodinations, and these cells are fated to become follicular cells only after metamorphosis, when they form classic thyroid follicles.1 The phylogenetic association of the thyroid gland and the gastrointestinal tract is evident in several functions. 327

PHYLOGENY, EMBRYOLOGY, AND ONTOGENY
Phylogeny
The phylogeny, embryogenesis,and certain aspects of thyroid function are closely interlinked with the gastroin­ testinal tract. The capacity of the thyroid to metabolize iodine and incorporate it into a variety of organic com­ pounds occurs widely throughout the animal and plant

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THYROID PHYSIOLOGY AND DIAGNOSTIC EVALUATION

I Pa

Pharyngeal floor

I Pa

II Pa

Thyroid anlage

II Pa

Figure 11-1 Thethyroid anlage. Left, Scanning electron micrograph of a mouse embryo at embryonic day 9, showing the area where the thyroid bud has invaginated, leaving behind the foramen cecum. The cranial direction is up. Right, A schematic view of the pharyngeal region of an embryo at the same stage. Pa, pharyngeal arch. (From De Felice M, Di Lauro R. Thyroid development and its disorders: genetic and molecularmechanisms. Endocr Rev. 2004;25:722-746. Copyright 2004 by the Endocrine Society.)

The salivary and gastric glands, like the thyroid, are capable of concentrating iodide in their secretions, although iodide transport in these sites is not responsive to stimulation by thyrotropin (thyroid­stimulating hormone [TSH]). The sali­ vary gland contains enzymes that are capable of iodinating tyrosine inthe presence of hydrogen peroxide, although it forms insignificant quantities of iodoproteins under normal circumstances.

the critical factors that are required for normal thyroid gland development.2,3 The roles of these various proteins are currently being evaluated with respect to the potential for defects in the synthesis or formation of the thyroid gland (see Chapter 13).

FunctionalOntogeny
The ontogeny of thyroid function and its regulation in the human fetus are fairly well defined.4 Future follicular cells acquire the capacity to form thyroglobulin (Tg) as early as the 29th day of gestation, whereas the capacities to con­ centrate iodide and synthesize thyroxine (T4) are delayed until about the 11th week. Radioactive iodine inadver­ tently given to the mother would be...