Stress (cont.)

During stress, the priorities of the secretions of the hypothalamo-pituitary peripheral-endocrine axes

are shifted in favor of the hypothalamo-pituitary-adrenocortical (HPA) axis.

During stress:

HPA

GHRHGHGnRHFSHLH

Hypothalmo-Pituitary-Thyroid System

Figure 13-1: Diagrammatic representation of the thyroid gland

Figure 13-2

Table 13.3Major Actions of Thyroid

Hormones• Calorigenesis

• Metabolism• Brain maturation

• Behavior• Growth & development

Figure 13-3

CNS

↓HYPOTHALAMUS

TRH

↓PITUITARY

↓TSH

↓THYROID GLAND↓ ↓ ↓T3 T4 rT3

TARGET CELLS

↓T4 T3

↓INTRACELLULAR (NUCLEAR) BINDING

↓METABOLI C RESPONSE

CLEARANCE

FREE &BOUND

(-)

(-)

3, 5, 3’, 5’ Tetraiodothyronine (thyroxine, T4)

3, 5, 3’ Triiodothyroine (T3)

Table 13-2: Some MORPHOLOGIC Changes in the Thyroid Gland with Aging

FOLLICLES:- Are distended- Change in color

- Epithelium flattened w/reduced secretion

Fewer mitoses

Increased connective tissue;

Fibrosis

Atherosclerotic changes

Table 13-2 (con’t.): Some SECRETORY Changes

in the Thyroid Gland with Aging

Simultaneously decreased secretion and metabolic

clearance of T4 with resulting essentially normal levels

Failure of up-regulation of

T3 nuclear receptors

peripheral conversion of T4 to T3

TSH levels in 10% of the elderly, associated

in antithyroid antibodies, present even in the absence of manifestations of hypothyroidism

circulating T3 levels but generally within

the normal (lower) range

Table 13-1: Some Critical Aspects of Thyroid Hormone Regulation

1. Major source of circulating T3 from peripheral deiodination of T4 (NOT from thyroid gland secretion)

2. The negative feedback at the pituitary anterior lobe is mainly through T4 (taken from circulation & converted into T3)

3. The peripheral deiodination of T4 depends on the physiological state of the organism. It allows an autonomy of response of the tissues to the hormones.

4. Deiodination can convert T4 (a less biologically active hormone) to T3 (a more active hormone). This conversion depends on the activity of the various deiodinating enzymes.

Figure 13-4

Basal Metabolic Rate

Basal Metabolic Rate

from birth to 70 years old

Table 13-5 In the Elderly, Thermoregulatory Insufficiency

Results from:

heat production,

body mass,

muscle activity,

shivering,

sweating response,

vasomotor responses,

temperature perception.

Table 13-6 Autoimmune Diseases of the Thyroid Gland

Characteristics Graves’ Disease Hashimoto’s Thyroiditis

Thyroid Status Hyperthyroid Hypothyroid

TSH Generally undetectable

Normal to elevated

T4, T3 (serum) Above normal Below normal

Antibodies(ABs) Stimulatory ABs compete with TSH at receptor sitesLoss of TSH control over thyroid function

Some ABs block TSH actions

Autoantibodies against thyroglobulin, T3, T4, thyroid destroy thyroid microsomal and nuclear components

Generally present

Generally present

Lymphocytic Invasion

Limited Marked

Female:Male Ratio

As high as 10:1 As high as 10:1