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Thyroid hormone signaling and its metabolic code have been studied extensively by Bianco AC. In his 2011 paper published in Endocrinology, Bianco highlights the importance of transthyretin and albumin in binding thyroid hormones, while emphasizing that only the free fractions of T4 and T3 are biologically active.

One of the key functions of T4 is to serve as a prohormone, regulated by three types of deiodinases. The outer ring monodeiodination yields 75% of the daily production of T3, which is the principal active hormone. On the other hand, monodeiodination of the inner ring results in reverse T3, which is biologically inactive. The proportioning of T4 between T3 and reverse T3 is crucial in determining the availability of active thyroid hormone.

The impact of thyroid hormone on the body extends beyond its role as a regulator of the basal metabolic rate and thermogenesis. It also affects heart rate, cardiac output, ventilation, systemic vascular resistance, and substrate mobilization. Furthermore, thyroid hormone plays a vital role in the central nervous system and skeletal development. Absence of the hormone during development leads to congenital hypothyroidism, characterized by poor brain development, short stature, and immature skeletal development. In adults, thyroid hormone is involved in bone remodeling, as well as the degradation of skin and hair.

Thyroid hormone exerts its actions by binding to specific thyroid hormone receptor subtypes. These receptors heterodimerize with RXR to regulate thyroid response elements on target genes, resulting in either induction or repression of gene expression in the presence or absence of T3, respectively.

Additional resources for understanding thyroid hormone signaling include Brent GA's 2012 paper on the mechanisms of thyroid hormone action and de Vries EM's 2015 review on the molecular basis of the non-thyroidal illness syndrome. Krude H and colleagues' 2015 publication provides insights into the treatment of congenital thyroid dysfunction.

At the end of this chapter, students should be able to answer the following questions:

1. Provide a description of the anatomy and microscopic anatomy of the adrenal gland, including the chromaffin cells of the adrenal medulla and the three zones of the adrenal cortex.
2. Explain the enzymatic reactions involved in the synthesis of norepinephrine and epinephrine, and how these reactions are regulated in the adrenal medulla.
3. Describe the overall sympathetic response to stress imposed on the body by utilizing the specific actions of catecholamines.
4. Discuss the first two common reactions of the steroidogenic pathway, their subcellular locations, and the function of StAR protein in the first reaction.
5. Compare the steroidogenic pathways within the zona glomerulosa, zona fasciculata, and zona reticularis in terms of common and zona-specific reactions.
6. Provide a description of the mechanism of action of glucocorticoids and mineralocorticoids, including the cross-reactivity of cortisol with the mineralocorticoid receptor and the mechanisms to prevent this.
7. Explain the multiple actions of cortisol throughout the body, including its role during normal development and physiology, as well as its involvement in the pathophysiology of Addison's disease and Cushing's syndrome.
8. Map out the hypothalamic-pituitary-adrenal axis, including the "loophole" in the feedback mechanisms that leads to excessive androgen production, such as in congenital adrenal hyperplasia, due to a specific enzyme deficiency in the zona fasciculata and cortisol synthesis.

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Bianco AC. Minireview: cracking the metabolic code for thyroid hormone signaling. Endocrinology. 2011;152:3306-3311.
transthyretin, and albumin. Only the free fractions of T4 and T3 are biologically active.
9.
T4 functions largely as a prohormone whose disposition is regulated by three types of deiodinases. Monodeiodination of the outer ring yields 75% of the daily production of T3, which is the principal active hormone. Alternatively, monodeiodination of the inner ring yields reverse T3, which is biologically inactive. Proportioning of T4 between T3 and reverse T3 regulates the availability of active thyroid hormone.
10.
Thyroid hormone is a major positive regulator of the basal metabolic rate and thermogenesis. Other important actions of thyroid hormone are increased heart rate, cardiac output, and ventilation and decreased systemic vascular resistance. Substrate mobilization and disposal of metabolic products are enhanced.
11.
Thyroid hormone action on the CNS and skeleton are crucial for normal growth and development. Absence of the hormone causes congenital hypothyroidism, characterized by poor brain development, short stature, and immature skeletal development. In adults, thyroid hormone supports bone remodeling and degradation of skin and hair.
12.
T3 binds to thyroid hormone receptor subtypes responsible for the various actions of thyroid hormone. The thyroid hormone receptor heterodimerizes with RXR to regulate thyroid response elements on target genes, resulting in induction or repression in the presence or absence of T3, respectively.
Brent GA. Mechanisms of thyroid hormone action. J Clin Invest. 2012;122:3035-3043.
de Vries EM, et al. The molecular basis of the non-thyroidal illness syndrome. J Endocrinol. 2015;225:R67-R81.
Krude H, et al. Treatment of congenital thyroid dysfunction: achievements and challenges. Best Pract Res Clin Endocrinol Metab. 2015;29:399-413.
Upon completion of this chapter the student should be able to answer the following questions: 1.
Describe the anatomy and microscopic anatomy of the adrenal gland, including the chromaffin cells of the adrenal medulla and the three zones of the adrenal cortex.
2.
Explain the enzymatic reactions involved in generating norepinephrine and epinephrine and integrate those reactions with the regulation of epinephrine synthesis and secretion by the adrenal medulla.
3.
Utilize the specific actions of catecholamines to explain an overall sympathetic response to a stress imposed on the body.
4.
Describe the first two common reactions of the steroidogenic pathway, and their subcellular locations, and the function of StAR protein in the first reaction.
5.
Compare the steroidogenic pathways within the zona glomerulosa, zona fasciculata, and zona reticularis with respect to common and zona-specific reactions.
6.
Describe the mechanism of action of glucocorticoids and mineralocorticoids, including the cross-reactivity of cortisol with the mineralocorticoid receptor, and the mechanism to prevent this.
7.
Integrate the multiple actions of cortisol throughout the body to explain the hormone’s role during normal development and physiology, and to describe the multiple aspects of the pathophysiology of Addison’s disease and Cushing’s syndrome.
8.
Map out the hypothalamic-pituitary-adrenal axis, including the “loophole” in the feedback mechanisms that leads to excessive androgen production (e.g., in congenital adrenal hyperplasia) in the face of an enzyme deficiency specific to the zona fasciculata and cortisol synthesis.
9.