Endocrine Diseases Flashcards
Endocrine system
The Endocrine System is a highly integrated and widely distributed group of organs that provide a system of communication and control in the body. The endocrine system uses chemical substances, hormones, to regulate and integrate body functions.
Hormones are of several different classes. They include:
* steroids (e.g. glucocorticoids, estrogen, progesterone),
* proteins (anterior pituitary hormones, e.g. adrenocorticotropic hormone [ACTH]),
* peptides (antidiuretic hormone [ADH], growth hormone),
* amino acids (thyroxine) and
* amines (epinephrine).
The endocrine system involves the hormone-producing organ, the hormone itself, and the receptor or target organ. One hormone may act on more than one target organ.
Classically the endocrine hormone producing organs are ductless glands that secrete hormones directly into the blood stream to be transported to, and exert their actions at, distant target organs (e.g. pituitary produces ACTH (corticotropin) that acts on the adrenal cortex), as opposed to the exocrine glands that secrete substances onto a surface of the body by way of a duct (e.g. sweat glands).
The definition of the Endocrine System has been widened now to include a more diverse group of cells in a wide variety of organs. Some hormones never enter the bloodstream but instead act locally on adjacent cells; a paracrine action (e.g. estrogen acting on the ovary). Hormones can also exert an autocrine action on the cell from which they were produced (e.g. insulin released from pancreatic β-cells can inhibit its release from the same cells).
Endocrine glands
The endocrine glands include: the hypothalamus, pituitary, and pineal body in the head; the thyroid, parathyroid and thymus of the throat area; the adrenal glands sitting atop the kidneys; the pancreas near the stomach (the pancreas is an exocrine gland too, secreting bile into the bile duct and protein and fat-digesting enzymes into the pancreatic duct for emptying into the stomach); and the gonads (male testes and female ovaries).
Endocrine diseases - general
All endocrinology can be divided into a problem of too much hormone, too little hormone or hormones acting at the wrong time.
Most endocrine diseases result from abnormalities in the producing organ. Because the endocrine system is a ‘body’ control system relatively small lesions in one organ can produce widespread and important clinical consequences. Several processes may disturb the normal activity of the endocrine system including:
* Impaired synthesis or release of hormone
* Abnormal interactions between hormones and their target tissues
* Abnormal responses of target organs to their hormones.
HYPOTHALAMIC-PITUITARY REGULATION / FEEDBACK REGULATION
The pituitary is the control centre of the endocrine system. The pituitary itself is under the influence and control of the brain and thus, the two main body control systems, neural and endocrine, work in tandem.
The pituitary receives signals from the hypothalamus, a region of the brain that receives incoming pathways regarding sight, smell, temperature, hunger, rage, and fear. In response to these signals it releases peptides called releasing factors or releasing hormones to a special group of blood vessels called the hypothalamo- hypophyseal portal system. This specially designed system carries both stimulatory and inhibitory peptides to the anterior pituitary to affect specific groups of cells within this portion of the gland. These cells then release hormones to specific target endocrine organs.
The endocrine system is thus often said to have three levels of control, tertiary (hypothalamic), secondary (pituitary), and primary endocrine organs (e.g. thyroid, adrenal, etc.). The challenge of endocrinology is to determine what level of control is abnormal in a given patient, as abnormalities at each level share many, but not all, clinical features.
The principle mode of internal control in the endocrine system is that of negative feedback, that is, the product of the target organ turns off the control organ. Thus, by measuring levels of both the final hormone and the hypothalamic and pituitary factors stimulating its production, an endocrinologist can often determine the site of abnormality. In clinical practice such sophisticated and costly tests are often not necessary as symptoms, features on physical examination, or radiologic investigations can localize these lesions more cheaply and efficiently.
The anterior pituitary releases 6 hormones under the control of stimulatory (+) or inhibitory (-) hypothalamic releasing factors: TSH, thyroid stimulating hormone; PRL, prolactin; ACTH, adrenocorticotropic hormone (corticotropin); GH, growth hormone; FSH, follicle stimulating hormone; LH, luteinizing hormone
PITUITARY
The pituitary gland is a small, bean-shaped structure that sits at the base of the brain within the sella turcica. It is connected to the hypothalamus physically and directly by a stalk composed of axons extending from the hypothalamus and indirectly through the rich venous plexus constituting the hypothalamo-hypophyseal portal system. The pituitary is composed of two morphologically and functionally distinct components: the anterior pituitary or adenohypophysis and the posterior pituitary or neurohypophysis.
The neurohypophysis is composed of modified glial cells (pituicytes) and axonal processes extending from nerve cell bodies in the supraoptic and paraventricular nuclei of the hypothalamus. These hypothalamic neurons produce two peptide hormones, ADH or antidiuretic hormone, and oxytocin (the latter stimulates contraction of smooth muscle in the pregnant uterus and mammary glands). ADH is released into the general circulation and acts on the collecting tubules of the kidney to promote the resorption of water. ADH deficiency causes diabetes insipidus characterized by excessive urination (polyuria).
The anterior lobe is composed of epithelial cells which in routine histological sections contain a variety of cells containing basophilic, eosinophilic, or poorly staining (chromophobic) cells. The staining properties of these cells are related to the presence of various hormones within their cytoplasm; immunohistochemical stains are now used to identify specific hormone-producing cells. The release of trophic hormones in the pituitary is under the control of factors produced in the hypothalamus. Most of the hypothalamic factors are stimulatory except for dopamine (which inhibits prolactin secretion) and somatostatin (which inhibits growth hormone release).
Symptoms of pituitary disease can be divided into:
* Hyperpituitarism or excess secretion of hormones
* Hypopituitarism or deficient secretion of hormones
* Local effects (usually due to an increase in mass of a local lesion or presence of a tumor).
HYPERPITUITARISM AND PITUITARY ADENOMAS
The most common cause of hyperpituitarism is an adenoma arising in the anterior lobe. These pituitary adenomas are classified on the basis of the hormone(s) produced by the neoplastic cells, which are detected by immunohistochemically staining tissue sections. Pituitary adenomas can be microadenomas (< 1 cm) or macroadenomas (>1 cm) and clinically they may be functional (associated with clinical manifestations of hormone excess) or silent (immunohistochemical demonstration of hormone production but no manifestations of hormone excess). Most adenomas consist of one cell type and produce one hormone (e.g. prolactinoma, GH-producing adenoma, corticotroph adenoma). Some pituitary adenomas can secrete two hormones, growth hormone and prolactin being the most common.
The usual pituitary adenoma is a well-circumscribed, soft lesion confined by the sella turcica. Microscopically pituitary adenomas are composed of relatively uniform, polygonal cells arrayed in sheets, cords, or papillae. Supporting connective tissue, or reticulin, is sparse. The nuclei of the neoplastic cells may be uniform or pleomorphic. The cytoplasm may be acidophilic, basophilic, or chromophobic depending on the type and amount of secretory product within the cell and is fairly uniform throughout (cellular monomorphism).
Prolactinomas are the most common type of hyperfunctioning pituitary adenoma and can range from small microadenomas to large, expanding tumors associated with considerable local mass effects. Hyperprolactinemia causes amenorrhea (absence of menstruation), galactorrhea (excessive or spontaneous flow of milk), loss of libido, and infertility. Prolactinomas are usually diagnosed at an earlier age in younger women in whom the clinical manifestations are more prominent than in men and older, postmenopausal women (e.g. amenorrhea). Hyperprolactinemia may be caused by other conditions, including pregnancy, high- dose estrogen therapy, renal failure, hypothyroidism, hypothalamic lesions, and DA-inhibiting drugs. Any mass in the suprasellar compartment may disturb the normal inhibitory effect of hypothalamic dopamine on prolactin secretion resulting in hyperprolactinemia (the stalk effect). Thus, mild elevations in serum PRL in someone with a pituitary adenoma do not necessarily indicate a PRL-secreting neoplasm.
Growth hormone (or somatotroph cell) adenomas are the second most common neoplasm. They are composed of densely or sparsely granulated cells which stain immunohistochemically for GH. If a GH- secreting tumor occurs in children before the epiphysis is closed in growing long bones then excessive levels of GH result in gigantism (a generalized increase in body size with disproportionately long arms and legs). In adults elevated levels of GH produces acromegaly (growth in soft tissues, skin, bones of the face, hands and feet). GH excess is also associated with abnormal glucose tolerance and diabetes mellitus, generalized muscle weakness, hypertension, arthritis, osteoporosis, and congestive heart failure. PRL is demonstrable in a number of GH-producing tumors and in some cases in sufficient quantities to produce signs of hyperprolactinemia.
Other anterior pituitary neoplasms include corticotroph cell adenomas (discussed below), gonadotroph adenomas, thyrotroph adenomas. Pituitary carcinomas are exceedingly rare.
Pituitary hormones may also be hormone negative (‘null cell’ adenomas). Silent and hormone-negative adenomas are more likely to come to attention at a later stage than those associated with endocrine abnormalities and hence, are more likely to be macroadenomas. The typical presentation is related to local mass effects including:
* radiologic abnormalities of the sella turcica (expansion, bony erosion, disruption of the diaphragma sellae)
* visual field abnormalities (e.g. bitemporal hemianopsia) due to expansion and compression of the optic
nerve fibres in the optic chiasm
* elevated intracranial pressure
* seizures or obstructive hydrocephalus
* cranial nerve palsy (with involvement of the cranial nerves)
* rarely, loss of consciousness and pituitary apoplexy (caused by acute hemorrhage into an adenoma). These lesions may also compromise the residual anterior pituitary sufficiently to produce hypopituitarism.
HYPOPITUITARISM
Hypofunction of the anterior pituitary may occur with loss or absence of 75% or more of the anterior pituitary functional cells. This may be congenital (very rare) or more likely result from a range of acquired abnormalities. Less frequently disorders that interfere with the delivery of hypothalamic releasing factors, e.g. hypothalamic tumors, may also cause hypofunction of the anterior pituitary. Most cases of hypofunction are caused by:
* non-functioning pituitary adenomas
* ischemic necrosis (e.g. postpartum necrosis of the anterior pituitary (Sheehan syndrome), elevated
intracranial pressure, traumatic injury, sickle cell anemia, shock)
* ablation by surgery or radiation
* inflammatory lesions (sarcoidosis, TB)
* trauma
* metastatic neoplasms
Clinical manifestations will depend on the specific hormone lacking, for example, growth failure in children who lack GH (pituitary dwarfism), amenorrhea and infertility due to GnRH deficiency, hypothyroidism (decreased TSH) or ACTH deficiencies (discussed below).
In general, abnormalities of the primary level are far more common than those at the pituitary or hypothalamic level. To demonstrate the interplay between abnormalities at the different levels of control we will examine one system in detail, the adrenal cortex.
Thyroid Gland
The thyroid gland sits anterior to the trachea just below the larynx. It consists of two lobes connected by an isthmus. It produces 3 hormones: T4 and T3 (by thyroid follicular cells), and calcitonin (produced by C cells). In response to thyroid hormone releasing hormone (TRH) released by the hypothalamus, thyroid stimulating hormone (TSH) is released from the anterior pituitary. This stimulates thyroid follicular cells to produce T4 and T3 from the stored precursor protein thyroglobulin. Secreted T3 and T4 inhibit release of TRH and TSH from the hypothalamus and pituitary, respectively.
TOO MUCH HORMONE - HYPERTHYROIDISM
Excess thyroid hormone (T4 and T3) causes a hypermetabolic state known as thyrotoxicosis, resulting in number of symptoms including heat intolerance, weight loss despite increased appetite, GI tract hypermotility and diarrhea, cardiac effects, neuromuscular effects, and ocular effects. Hyperthyroidism occurs secondary to a number of conditions:
Graves disease – an autoimmune condition resulting in thyrotoxicosis, opthalmopathy, and infiltrative dermopathy
“toxic” multinodular goitre
“toxic” thyroid adenoma
Pituitary adenoma (TSH secreting)
Iodine excess
Laboratory diagnosis of hyperthyroidism will show decreased TSH (majority of cases – notable exception is TSH secreting pituitary adenoma) and increased free T4 and T3 levels.
TOO LITTLE HORMONE - HYPOTHYROIDISM
Defined as decreased circulating T4 and T3 hormones due to structural or functional abnormality interfering with their production. Clinical manifestations include sensitivity to cold, fatigue, weight gain, constipation, muscle weakness, depression, and decreased heart rate (bradycardia). Congenital hypothyroidism may result in “cretinism”, abnormalities in the skeletal and CNS resulting in mental retardation, short stature etc. Long- standing, undiagnosed hypothyroidism may rarely result in “myxedema”, a potentially life-threatening complication.
Causes of hypothyroidism:
Dietary deficiency of iodine
Autoimmune disease, including Hashimoto thyroiditis
Iatrogenic causes such as radiation therapy or radioactive iodine therapy
Drug effect
Developmental anomalies (rare)
Pituitary failure
Laboratory diagnosis of hypothyroidism will show increased TSH and decreased free T4 and T3 levels
Thyroid neoplasms
Adenomas: typically round and solitary, and usually non-functional. Occasionally will produce thyroid hormone resulting in hyperthyroidism.
Carcinomas:
Papillary carcinoma (most common thyroid malignancy)
Follicular carcinoma
Anaplastic carcinoma
Medullary carcinoma
ADRENAL CORTEX
The adrenal cortex produces three groups of steroid hormones - glucocorticoids, mineralocorticoids, and sex steroids. These involve control of sugar-protein metabolism, water-electrolyte balance, and sexual function, respectively.
TOO MUCH HORMONE - ADRENOCORTICAL EXCESS
