resorption and a consequent increase in blood calcium ion concentration.

In the kidneys, PTH prevents urinary calcium loss; thus, ions are returned to the bloodstream.

PTH also controls calcium uptake in the intestines indirectly by modulating kidney production of vitamin D, which is essential for calcium absorption.

Increased levels of PTH cause an elevation in plasma calcium concentration; however, it takes several hours for this level to peak. The concentration of PTH in the blood is also controlled by plasma calcium levels.

•Calcitonin acts as an antagonist to PTH.

•Unlike PTH, calcitonin is fast acting, and since it binds directly to receptors on osteoclasts, it elicits a peak reduction in blood calcium levels within one hour.

•Calcitonin inhibits bone resorption, thus reducing calcium ion levels in the blood. High levels of calcium ions in the blood stimulate calcitonin release.

Absence of parathyroid glands is not compatible with life.

Suprarenal Glands

The suprarenal glands (adrenal glands in some animals) are invested by a connective tissue capsule (see Table 10-2 and Graphics 10-2 and 10-3). The glands are derived from two different embryonic origins, namely, mesodermal epithelium, which gives rise to the cortex, and neuroectoderm, from which the medulla originates. The rich vascular supply of the gland is conveyed to the interior in connective tissue elements derived from the capsule.

E N D O C R I N E S Y S T E M 233

These glucocorticoids regulate carbohydrate metabolism, facilitate the catabolism of fats and proteins, exhibit anti-inflammatory activity, and suppress the immune response.

•The innermost region of the cortex, the zona reticularis, is arranged in anastomosing cords of cells with a rich intervening capillary network.

Zona reticularis cells secrete weak androgens that promote masculine characteristics.

Medulla

Parenchymal cells of the medulla, derived from neural crest material, are disposed in irregularly arranged short cords surrounded by capillary networks. They contain numerous granules that stain intensely when the freshly cut tissue is exposed to chromium salts. This is referred to as the chromaffin reaction, and the cells are called chromaffin cells. There are two populations of chromaffin cells that secrete the two hormones (see Table 10-2) of the suprarenal medulla, mainly

•epinephrine (adrenaline) or

•norepinephrine (noradrenaline).

Secretion of these two catecholamines is directly regulated by preganglionic fibers of the sympathetic nervous system that impinge on the postganglionic sympathetic neuron-like chromaffin cells, which are considered to be related to postganglionic sympathetic neurons (see Graphic 10-3). Catecholamine release occurs in physical and psychological stress. Moreover, scattered, large postganglionic sympathetic ganglion cells in the medulla act on smooth muscle cells of the medullary veins, thus controlling blood flow in the cortex.

Cortex

The cortex is subdivided into three concentric regions or zones that secrete specific hormones (see Table 10-2). Control of these hormonal secretions is mostly regulated by ACTH from the pituitary gland.

•The outermost region, just beneath the capsule, is the zona glomerulosa, where the cells are arranged in arches and spherical clusters with numerous capillaries surrounding them.

Cells of the zona glomerulosa secrete aldosterone, a mineralocorticoid that acts on cells of the distal convoluted tubules of the kidney to modulate water and electrolyte balance.

•The second region, the zona fasciculata, is the most extensive. Its parenchymal cells, usually known as spongiocytes, are arranged in long cords, with numerous capillaries between the cords.

•Zona fasciculata cells secrete cortisol and corticosterone.

Pineal Body

The pineal body (epiphysis) is a projection of the roof of the diencephalon (see Table 10-2 and Graphic 10-2). The connective tissue covering of the pineal body is pia mater, which sends trabeculae and septa into the substance of the pineal body, subdividing it into incomplete lobules. Blood vessels, along with postganglionic sympathetic nerve fibers from the superior cervical ganglia, travel in these connective tissue elements. As the nerve fibers enter the pineal body, they lose their myelin sheath. The parenchyma of the pineal body is composed of pinealocytes and neuroglial cells.

•The pinealocytes form communicating junctions with each other and manufacture melatonin. Interestingly, melatonin is manufactured only at night.

•Neuroglial cells provide physical and nutritional support to pinealocytes.

•The pineal body receives indirect input from the retina, which allows the pineal to differentiate between

day and night, and, in that manner, assists in the establishment of the circadian rhythm.

•The extracellular spaces of the pineal body contain calcified granular material known as brain sand (corpora arenacea), whose significance, if any, is not known.

E N D O C R I N E S Y S T E M 235

It is unclear how the pineal gland functions in humans, but it does exert an affect on the control of the circadian rhythm. Nonetheless, melatonin is used to treat jet lag and in regulating emotional responses related to shortened daylight during winter, a condition called seasonal affective disorder (SAD).

Pituitary Gland

Galactorrhea is a condition in which a male produces breast milk or a woman who is not breast-feeding produces breast milk. In men, it is often accompanied by impotence, headache, and loss of peripheral vision and in women by hot flashes, vaginal dryness, and an abnormal menstrual cycle. This rather uncommon condition is usually a result of prolactinoma, a tumor of prolactin-producing cells of the pituitary gland. The condition is usually treated by drug intervention or surgery, or both.

Postpartum pituitary infarct is a condition due the pregnancy-induced enlarging of the pituitary gland and its concomitant increase in its vascularity. The high vascularity of the pituitary increases the chances of a vascular accident, such as hemorrhage, which results in the partial destruction of the pituitary gland. The condition may be severe enough to produce Sheehan’s syndrome, which is recognized by the lack of milk production, the loss of pubic and axillary hair, and fatigue.

Pituitary Somatotrope Adenoma

Pituitary somatotrope adenoma is one of the pituitary adenomas, benign tumors, that are more common in adults than in children. Somatotrope adenomas involve proliferation of acidophils, which produce an excess of growth hormones which, in children, result in gigantism, whereas in adults it results in acromegaly. These acidophils grow slowly and usually do not grow outside the sella turcica. Individuals afflicted with untreated

acromegaly frequently suffer from complications that increase their chance of succumbing to cardiovascular, cerebrovascular, and respiratory problems. These individuals also present with hypertension.

This is a photomicrograph from the pituitary gland of a patient with pituitary somatotrope adenoma. Note that the adenoma cells are arranged in ribbons and cords. (Reprinted with permission from Rubin R, Strayer D, et al., eds. Rubin’s Pathology. Clinicopathologic Foundations of Medicine, 5th ed. Baltimore: Lippincott Williams & Wilkins, 2008, p. 938.)

Thyroid Gland

Graves’ disease is caused by binding of autoimmune IgG antibodies to TSH receptors thus stimulating increased thyroid hormone production (hyperthyroidism). Clinically, the thyroid gland becomes enlarged, and there is evidence of exophthalmic goiter (protrusion of the eyeballs).

This photomicrograph is from the thyroid gland of a patient with Graves’ disease. Note that the follicular cells are high columnar hyperplastic cells enclosing pinkish colloid that is scalloped along its periphery. (Reprinted with permission from Rubin R, Strayer D, et al., eds. Rubin’s Pathology. Clinicopathologic Foundations of Medicine, 5th ed. Baltimore: Lippincott Williams & Wilkins, 2008, p. 946.)

Parathyroid Gland

Hyperparathyroidism may be due to the presence of a benign tumor causing the excess production of parathyroid hormone (PTH). The high levels of circulating PTH cause increased bone resorption with a resultant greatly elevated blood calcium. The excess calcium may become deposited in arterial walls and in the kidneys, creating kidney stones.

Suprarenal Gland

Addison’s disease is an autoimmune disease, although it may also be the aftermath of tuberculosis. It is

characterized by decreased production of adrenocortical hormones due to the destruction of the suprarenal cortex, and without the administration of steroid treatment, it may have fatal consequences.

This photomicrograph of the adrenal gland of a patient with Addison’s disease displays cortical fibrosis and inflammation, as well as a mass of atrophic cortical cells. (Reprinted with permission from Rubin R, Strayer D, et al., eds. Rubin’s Pathology. Clinicopathologic Foundations of Medicine, 5th ed. Baltimore: Lippincott Williams & Wilkins, 2008, p. 962.)

Type 2 polyglandular syndrome, a hereditary disorder, affects the thyroid and suprarenal glands in such a fashion that they are underactive (although the thyroid may become overactive). Frequently, patients with this disorder also develop diabetes.

Hormones Its and Gland Pituitary• 1-10 GRAPHIC

Glands Endocrine • 2-10 GRAPHIC

238 E N D O C R I N E S Y S T E M

Thyroid

Gland

Follicular cell

Parafollicular

cell

Parathyroid Gland

Oxyphil cell

Chief cell

Capsule

Pineal

Body

Pinealocytes

Z. reticularis

⎞

Z. fasciculata

Z. glomerulosa

Capsule

Capsule

Neuroglial cell

E N D O C R I N E S Y S T E M 239

Preganglionic sympathetic neuron and fiber

Postganglionic sympathetic neuron and fiber

Dorsal root ganglion

Sympathetic Collateral chain ganglion ganglion

Stomach, small intestine,

large intestine Medulla of suprarenal gland

Gland Suprarenal the of Medulla the and Viscera the of Innervation Sympathetic• 3-10 GRAPHIC

Gland y Pituitar• 1-10 PLATE

}Hypothalamus

Pars tuberalis

Infundibular stem

Pars intermedia

Pituitary gland

FIGURE 1

Gland y Pituitar• 1-10 PLATE

Gland y Pituitar• 2-10 PLATE

Pars nervosa

Pars intermedia

}

Acidophil Basophil

Gland Parathyroid Gland, hyroid • T3-10 PLATE

Gland uprarenal • S4-10 PLATE

Body Pineal Gland, uprarenal • S5-10 PLATE

FIGURE 1. Pituitary gland. Pars anterior. Electron microscopy. ×4,950.

Although considerable controversy surrounds the precise fine structural identification of the cells of the pars anterior, it is reasonably certain that the several cell types presented in this electron micrograph are acidophils, basophils, and chromophobes, as

observed by light microscopy. The acidophils are somatotropes (S) and mammotropes (M), whereas only two types of basophils are included in this electron micrograph, namely, type II gonadotropes (G2) and thyrotropes (T). The chromophobes (C) may be recognized by the absence of secretory granules in their cytoplasm. (From Poole M. Cellular distribution within the rat adenohypophysis: a morphometric study. Anat Rec 1982;204:45–53.)

FIGURE 1. Pituitary gland. Rat. Electron microscopy. ×8,936.

The pars distalis of the rat pituitary houses various cell types, two of which are represented here. The granule-containing gonadotrophs (GN) are surrounded by nongranular folliculostellate cells

(FS), whose processes are demarcated by arrows. The functions of folliculostellate cells are in question, although some believe them to be supportive, phagocytic, regenerative, or secretory in nature. (From Strokreef JC, Reifel CW, Shin SH. A possible phagocytic role for folliculo-stellate cells of anterior pituitary following estrogen withdrawal from primed male rats. Cell Tissue Res 1986;243:255–261.)