Chapter 18 The Endocrine System
Hormones are biologically active substances secreted by one cell that stimulate other cells. Traditionally this term was reserved for endocrine substances (i.e., secreted into the blood and carried by circulation to their distant target organs). This concept was broadened and today includes a variety of substances that exert:
Figure 18-1 Hormonal stimulation. A, Endocrine. The hormones are carried by blood from the cell that has produced the hormone to the distant target. B, Paracrine. The hormone produced by one cell acts on an adjacent cell. C, Autocrine. The hormone acts on the cell that has produced it. D, Neurocrine. The hormone released from a nerve cell acts on an endocrine cell.
In general, peptide and amine hormones are stored inside the cells of their origin in the form of dense neuroendocrine granules that can be seen by electron microscopy. These hormones act on receptors on the plasma membrane of target cells, which in turn activate a signaling system in the cytoplasm. The impulse is transmitted from the plasma membrane to the DNA by secondary messengers. In contrast to these hormones, steroids are not stored in granules but are synthesized on external stimulation by trophic hormones (e.g., adrenocorticotropic hormone [ACTH] stimulates the synthesis of glucocorticoids). Steroid hormones have receptors in the nucleus of their target cells, and their action on the nuclear DNA does not require activation of a cytoplasmic messenger system. See Fig. 18-2.
The enlargement of endocrine glands may be accompanied by overproduction of hormones, no obvious hormonal changes, or reduced hormonal output. For example, thyroid enlargement in Graves disease is associated with hyperthyroidism. Nodular goiter is most often euthyroid. Anaplastic carcinoma may completely destroy the normal thyroid and cause hypothyroidism.
The pituitary is located in the sella turcica, a concavity of the sphenoid bone that forms a part of the base of the skull. Enlargement of the pituitary can cause an expansion of the sella turcica that can be seen by x-ray.
The pituitary is attached to the brain by a stalk, composed of blood vessels of the pituitary portal system and axonal extensions of hypothalamic nerves. Transection of the pituitary stalk causes hypopituitarism. It will hinder the influx of blood that contains the hypothalamic-releasing factors (i.e., neuropeptides that normally stimulate the cells in the anterior lobe of the pituitary). The transection of axons that serve as conduits for the transport of oxytocin and antidiuretic hormone (ADH) from the hypothalamus into the posterior lobe of the pituitary will prevent the entry of these hormones into the blood and thus cause diabetes insipidus.
Enlargement of the pituitary will cause compression of the optic chiasm, which is overlying the membranous covering of the sella turcica. Compression of the central portion of the chiasm leads to a loss of lateral visual fields of both eyes, known as bilateral hemianopsia.
Cells that do not react with antibodies to any of the previously mentioned hormones are called null cells and represent either undifferentiated stem cells or exhausted and nonfunctioning cells. Some nonfunctioning cells have prominent eosinophilic cytoplasm and contain numerous mitochondria. These cells are called oncocytes. The posterior lobe of the pituitary is composed of axonal processes of hypothalamic neurons and does not contain hormone-producing cells.
Most pituitary tumors are monoclonal and are composed of a single cell type corresponding to one of the six cell types found in the normal anterior lobe of the pituitary. Axons of the posterior pituitary do not form tumors.
Most pituitary tumors (>95%) are benign and classified as adenomas. Most adenomas are composed of a single cell type and secrete only one hormone. Prolactinomas, which account for approximately 30% of all pituitary tumors, are the most common pituitary neoplasm.
Approximately 80% of all pituitary tumors are hormonally active. In the remaining 20% of cases, the pituitary tumors are composed of hormonally inactive cells, which may compress the normal gland and cause hypopituitarism. Small clinically undiagnosed pituitary tumors may be found accidentally in 20% of routine adult autopsies.
In normal circumstances, pituitary lactotrophs are inhibited by dopamine and therefore do not secrete prolactin. Many cases of hyperprolactinemia are related to a loss of this dopaminergic inhibition. Bromocriptine, a dopamine agonist, will inhibit prolactin secretion and cause regression of lactotroph hyperplasia and even microscopic prolactinomas. Larger tumors that do not respond must be removed surgically, usually by a transethmoidal approach.
The most prominent findings are the marked enlargement of hands and feet, nose, and jaws (“acra,” i.e., protruding terminal parts). These externally visible changes are accompanied by internal organomegaly and metabolic disorders (diabetes, hypertension, etc.). The most common findings are illustrated in Fig. 18-3.
Cushing disease is hypercortisolism caused by an ACTH-secreting tumor. Because the ACTH molecule contains a fragment that has a melanocyte-stimulating function, the disease is associated with hyperpigmentation of the skin.
These tumors do not produce distinct clinical syndromes and are usually diagnosed only after they have attained a size that will cause a mass effect. Menstrual abnormalities, infertility, and various nonspecific hormonal changes are found in some patients.
Sheehan syndrome is also known as postpartum pituitary necrosis. Previously it was the most common form of ischemic necrosis of the pituitary, but it is rare today. It develops due to massive blood loss at the time of delivery, causing hypoperfusion of the pituitary that has undergone physiologic hyperplasia during pregnancy. Symptoms include hypothyroidism, adrenal insufficiency, and amenorrhea.
This term is applied to a variety of conditions in which the sella turcica appears “empty.” In primary empty sella syndrome, which rarely presents with hypopituitarism, the pituitary atrophy is related to a compression by the cerebrospinal fluid and arachnoidea that invaginate into the sella through a defect in the diaphragm. Secondary empty sella is a consequence of surgical intervention or radiation therapy.
Diabetes insipidus is a syndrome characterized by polyuria, polydipsia, and renal loss of water due to a deficiency of ADH. It may be caused by injury of the hypothalamus, pituitary stalk, or posterior pituitary.
This syndrome, characterized by excessive renal retention of water and dilutional hyponatremia, is caused by hyperproduction of ADH. The most common causes of ADH overproduction are small cell lung cancer, chronic lung disease, and hypothalamic lesions.
Craniopharyngiomas are tumors originating from remnants of the Rathke pouch, the embryonic anlage of the anterior pituitary. These tumors occur in children and young adults, and they are located in the suprasellar space, causing lesions of the hypothalamus and the pituitary stalk.
The thyroid develops during early embryonic life from the outpouching of the pharyngeal epithelium at the base of the tongue. This epithelium proliferates and forms the thyroglossal duct, which extends caudally, finally forming the thyroid on the anterior side of the neck. The thyroglossal duct involutes normally during fetal life, but if this involution is not complete its remnants give rise to thyroglossal duct cysts.
Thyroxine (tetraiodothyronine or T4) is formed from thyroglobulin by follicular cells. Follicular cells stimulated by TSH pinocytose thyroglobulin and transform it into T4 and, to a lesser extent, triiodothyronine (T3). T4 and T3 are released into the blood, where they circulate predominantly bound to thyroid-binding globulin (TBG) but also in a free form.
Goitrogens are substances such as propylthiourea that interfere with the synthesis of T4 and T3. In an effort to compensate for the reduced production of T4 and T3, thyroid follicles enlarge and become lined by hyperplastic epithelium. Inefficient synthesis of T3/T4 leads to an accumulation of colloid in follicles. These dilatated follicles cause enlargement of the thyroid known as goiter or struma.
Yes. Some goiters contain hyperfunctioning thyroid cells, which form nodules detectable by radioactive iodine scanning (“hot nodules”). Solitary hyperfunctioning nodules in an otherwise normal thyroid represent benign tumors (adenomas) that account for a small percentage of hyperthyroidisms.
Symptoms of hyperthyroidism are caused by hypermetabolism and excessive stimulation of the sympathetic system. Increased metabolic rate is accompanied by hyperactivity and subsequent fatigue, heat intolerance, and weight loss. The most important signs and symptoms related to major organ systems are:
No. Exophthalmos is found only in patients with Graves disease. It is associated with lymphocytic infiltrates in the retroorbital tissues. External eye muscles are particularly affected and appear swollen. This enlargement of the retroorbital tissue and orbital muscles leads to proptosis (anterior displacement of the eyeball). The weakness of eye muscles results in functional disturbances such as diplopia and inability to read. During physical examination, these patients show conjunctival congestion and palpebral symptoms (“lid lag” and “lid retraction”).
The most useful tests are based on the measurements of TSH, T4, and T3 (total and free form). Increased serum TBG (in pregnancy) or decreased TBG (in cirrhosis) may influence the concentration of T3/T4 in blood. Radioactive iodine uptake is followed by a thyroid scan to determine whether the entire thyroid is hyperfunctioning or whether the disease is caused by a hyperfunctioning nodule.
Hashimoto (autoimmune) thyroiditis is the most common cause of hypothyroidism in the United States, as well as in other developed countries that use iodized salt. In some underdeveloped mountainous regions of Asia (Himalayas) or South America (Andes), iodine deficiency is a significant cause of goiter, which may be accompanied by hypothyroidism.
Cretinism is a term used for hypothyroidism of infancy and early childhood. Previously, it was endemic in iodine-deficient areas. Today it is rare in the United States and is most often caused by congenital agenesis of the thyroid or inborn errors of iodine metabolism and thyroid hormone synthesis.
Hypothyroidism of infancy and early childhood retards the somatic growth and affects the development of the central nervous system. These children have short stature and are mentally retarded. Their faces have coarse features and a protruding tongue.