Saturday, April 09, 2005


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Anterior Pituitary Hormones
1) Adrenocorticotropic hormone (ACTH) - stimulates the adrenal cortex to secrete cortisol and several weak androgens. The ACTH-cortisol axis is central to the response to stress, and in the absence of ACTH, the adrenal cortex atrophies and secretion of cortisol virtually ceases.
2) Alpha- and beta-melanocyte stimulating hormone (MSH) - cause hyperpigmentation of skin and are only significant in disorders in which ACTH levels are markedly elevated (Addison's disease).
3) thyroid stimulating hormone (TSH) - regulates the structure and function of the thyroid gland and stimulates synthesis and release of thyroid hormones. TSH synthesis and secretion are controlled by the hypothalamic hormone, Thyrotropin Releasing Hormone (TRH), and by circulating thyroid hormone from the periphery.
4) Luteinizing hormone (LH) and Follicle Stimulating Hormone (FSH) - in women stimulate ovarian follicular development and ovulation. In men, FSH is essential for spermatogenesis, and LH stimulates testosterone biosynthesis.
5) Growth Hormone (GH) (somatotropine) – the major actions is stimulation of somatic growth and regulation of metabolism. Somatostatin is the major inhibitor of the synthesis and secretion of GH.
6) Prolactine (PRL) - the major function is regulation of milk production. PRL release also occurs with stress and sexual activity. PRL is the most frequent hormone produced in excess by pituitary tumors.

Posterior Pituitary Hormones
1) Antidiuretic hormone (ADH, vasopressin) – the major action is to promote water conservation by the kidney. At high concentrations it also causes vasoconstriction. ADH release is stimulated by pain, stress, exercise, hypoglycemia, cholinergic agonists, beta-adrenergic agonists, angiotensin, prostaglandins, etc. Alcohol, alpha-adrenergic agonists, glucocorticoids, etc, inhibit ADH secretion.
2) Oxytocin - stimulates contraction of uterine smooth muscle cells, and uterine sensitivity to oxytocin increases throughout pregnancy; also stimulates milk delivery from the breast during lactation.

The endocrine system in females and males. Image from Purves et al., Life: The Science of Biology, 4th Edition,
Syndromes of excessive secretion of GH (hypersomatotropism) nearly always due to a pituitary adenoma of the somatotrophs.
Drugs of treatment:
Bromocriptine mesylate - to 15 mg/day orally in divided doses
Octreotide - a long-acting somatostatin analog has been shown to suppress GH secretion effectively in patients refractory to bromocriptine. Side effects - gastritis, gallstones, cholangitis, jaundice, malabsorption of vitamin B12.

(Central Diabetes Insipidus; Vasopressin-Sensitive Diabetes Insipidus)
A temporary or chronic disorder of the neurohypophyseal system due to deficiency of vasopressin (antidiuretic hormone, ADH) and characterized by excretion of excessive quantities of very dilute (but otherwise normal) urine and by excessive thirst.
Drugs of treatment:
Hormonal therapy: Because vasopressin is a small peptide, it is ineffective when administered orally. Aqueous vasopressin - s.c. or IM in doses of 5 to 10 u. each 6 h or less.
Synthetic vasopressin (Pitressin ®) - bid to qid as a nasal spray, with the dosage and interval designed for each patient.
DDAVP® (desmopressin acetate, 1-deamino-8- d -arginine vasopressin), a synthetic analog of arginine vasopressin, has prolonged antidiuretic activity lasting for 12 to 24 h, administered intranasally, s.c., or IV. Desmopressin acetate is the preparation of choice for both adults and children. The usual dosage in adults is 0.1 to 0.4 mL (10 to 40 µg), with most requiring 0.2 mL/day in 2 divided doses. For children age 3 mo to 12 yr, the usual dosage range is 0.05 to 0.3 mL/day. Overdosage can lead to fluid retention and decreased plasma osmolality, possibly resulting in convulsions in small children. In such instances, furosemide may be used to induce diuresis. Headache may be a troublesome side effect but generally disappears if the dosage is reduced. Infrequently, desmopressin acetate may cause a slight increase in BP. Desmopressin acetate may also be used IV in acute situations.
Lypressin (lysine-8-vasopressin) - a synthetic agent, given by nasal spray as required at 3- to 8-h intervals.
Vasopressin tannate in oil - IM in a dose of 0.3 to 1 mL (1.5 to 5 u.) controls symptoms up to 96 h.

Nonhormonal therapy: At least 2 types of drugs are useful in reducing polyuria: (1) various diuretics, primarily thiazides, and (2) ADH-releasing drugs such as chlorpropamide, carbamazepine, and clofibrate. The thiazides paradoxically reduce urine volume in DI, primarily as a consequence of reducing extracellular fluid (ECF) volume and increasing proximal tubular resorption.
Chlorpropamide (3 to 5 mg/kg orally once or twice/day) causes some release of ADH, also potentiates the action of ADH on the kidney.
Clofibrate 500 to 1000 mg orally bid or carbamazepine 100 to 400 mg orally bid is recommended for adults only.
Prostaglandin inhibitors such as indomethacin (1.5 to 3.0 mg/kg/day orally in divided doses) effective in reducing urine volume perhaps by decreasing renal blood flow and glomerular filtration rate.

Iodide, ingested in food and water, is actively concentrated by the thyroid gland, converted to organic iodine by peroxidase, and incorporated into tyrosine in intrafollicular thyroglobulin. The tyrosines are iodinated at either one (monoiodotyrosine, MIT) or two (diiodotyrosine, DIT) sites and then coupled to form the active hormones (diiodotyrosine + diiodotyrosine --> tetraiodothyronine [thyroxine, T4]; diiodotyrosine + monoiodotyrosine --> triiodothyronine [T3]). Thyroglobulin, a glycoprotein containing T3 and T4 within its matrix. Lysosomes containing proteases cleave T3 and T4 from thyroglobulin, resulting in release of free T3 and T4.

Physiologic Effects of Thyroid Hormone
(1) increase protein synthesis in virtually every body tissue (T3 and T4 enter cells, bind to discrete nuclear receptors, and influence the formation of mRNA); (2) increase O2 consumption by increasing the activity of the Na+-K+ ATPase (Na pump), primarily in tissues responsible for basal O2 consumption (ie, liver, kidney, heart, and skeletal muscle). The increased activity of Na+-K+ ATPase is secondary to increased synthesis of this enzyme; therefore, the increased O2 consumption is also probably related to the nuclear binding of thyroid hormone. T3 is at least 3 times more active than T4, although T4 itself is biologically active.

(Thyrotoxicosis; Toxic Diffuse Goiter; Graves' Disease; Basedow's Disease)
Drugs of treatment
Iodine - inhibits the release of T3 and T4 organification of iodine, a transitory effect lasting from a few days to a week ("escape phenomenon"). Iodine is generally not used for routine treatment of hyperthyroidism. The usual dosage is 2 to 3 drops of a saturated potassium iodide solution orally tid or qid (300 to 600 mg/day), or 0.5 gm sodium iodide in 1 L 0.9% sodium chloride solution given IV slowly q 12 h. Complications include inflammation of the salivary glands, conjunctivitis, and skin rashes.
Propylthiouracil and methimazole - decrease organification and impair the coupling reaction.
Propylthiouracil (but not methimazole) in doses >800 mg/day also inhibits the peripheral conversion of T4 to T3. The usual starting dosage for propylthiouracil is 100 to 150 mg orally q 8 h, and for methimazole 10 to 15 mg orally daily. Maintenance doses can be continued for one year or many years depending on the clinical circumstances. Carbimazole is rapidly converted to methimazole. The usual starting dosage is 10 to 15 mg orally q 8 h; maintenance dosage is 10 to 15 mg/day.
Adverse effects - allergic reactions, nausea, loss of taste, and, in <1% of patients, a reversible agranulocytosis.
B-Adrenergic blocking drugs: Symptoms and signs of hyperthyroidism due to adrenergic stimulation may respond to Propranolol.
Radioactive sodium iodine - the treatment of choice in patients >40 yr of age. Dosage of I is difficult to gauge, and the response of the gland cannot be predicted.

The characteristic reaction to thyroid hormone deficiency in the adult.
Drugs of treatment
A variety of thyroid hormone preparations are available for replacement therapy: synthetic preparations of thyroxine, liothyronine (triiodothyronine), combinations of the 2 synthetic hormones, and desiccated animal thyroid. Synthetic preparations of T4 (L-thyroxine) are preferred; the average maintenance dosage is 100 to 125 µg/day orally. Absorption is fairly constant at about 90 to 95% of the dose.
T3 (liothyronine sodium) should not be used alone for long-term replacement because its rapid turnover requires that it be taken bid or tid.

The adrenal cortex produces androgens, glucocorticoids (cortisol), and mineralocorticoids (aldosterone).
The medulla produces catecholamines (mostly epynephrin)
The principal hormones produced by the adrenal cortex are cortisol (hydrocortisone), aldosterone, and dehydroepiandrosterone (DHEA). Adults secrete about 20 mg of cortisol, 2 mg of corticosterone (which has similar activity), and 0.2 mg of aldosterone daily. Although considerable quantities of androgens (primarily DHEA and androstenedione) are normally produced by the adrenal cortex, these exert their chief physiologic activity after conversion to testosterone and dihydrotestosterone.
The physiological effects of steroids:
1) Increased levels of serum glucose
2) Increased lipids deposition
3) Increased catalysis of proteins
4) Increased platelets aggregation
5) Kaliuretic effect
6) Na retention effect
7) Increased Ca releasing from the bones
8) CNS stimulation
9) cyclooxygenase (COX) inhibition
10) Inhibition of white blood cell (WBC) and mast cell activity

Steroids replacement therapy is useful.
Glucocorticoids are divided on classes by the time of their action:
1. Short-acting : hydrocortisone, prednisone, prednisolone, fluotorton, methylprednisolone.
2. Moderate-acting : thriamsynolone, paramethasone, fluprednisone.
3. Long-acting : betamethasone, dexamethasone.
Adverse effects of steroids:
1) leukopenia, thrombocytosis, increased coagulation
2) hypokalemia, hypernatremia, hypercalcemia, hyperglycemia
3) osteoporosis, in children –impaired bones growth rate
4) immunosuppressive state and secondary infections
5) peptic ulcer, obesity, muscular atrophy
6) hypertension, edemas
7) impaired sexual function
8) CNS hyperstimulation (agitation, irritability, delirium)

Clinical abnormalities due to chronic exposure to excesses of cortisol or related corticosteroids.
Drugs of treatment
Adrenal inhibitors:
Metyrapone - 250 mg qid orally, increasing to a maximum of no more than 2 gm/day;
Aminoglutethimide - 250 mg bid orally, increasing to a maximum of no more than 2 gm/day;
Mitotane (o,p-DDD) - 0.5 gm qid orally, increasing to a maximum total dose of 8 to 12 gm/day
Ketoconazole - blocks steroid synthesis in all systems
Adverse reactions – the most problematic is inhibition of synthesis of all groups of steroids is the body.

A tumor of chromaffin cells that secrete catecholamines, causing hypertension.
Drugs of treatment
Usually treatment includes the combination of alpha- and beta-adrenergic blocking agents (phenoxybenzamine 40 to 160 mg/day and propranolol 30 to 60 mg/day, orally in divided doses).
The infusion of trimethaphan camsylate or sodium nitroprusside useful in case of hypertensive crisis.
Metyrosine - orally, may be used alone or in combination with an alpha-adrenergic blocking agent (phenoxybenzamine); the optimally effective dosage is 1 to 4 gm/day in divided doses, should be given for at least 5 to 7 days before surgery.
Labetalol - an agent with both A- and B-adrenergic blocker properties, has been used at a dosage of 200 mg/day orally in divided doses.

A syndrome characterized by hyperglycemia resulting from impaired insulin secretion and/or effectiveness
Classification and Pathogenesis
Insulin-dependent diabetes mellitus (IDDM, type I DM) is clinically characterized by hyperglycemia and a propensity to DKA. Its control requires chronic insulin treatment. The IDDM is associated with islet cell autoantibodies that selectively bind to beta-cells and cause their destruction.

Non-insulin-dependent diabetes mellitus (NIDDM, type II DM) is characterized clinically by hyperglycemia that is not associated with a propensity to DKA. It is commonly associated with obesity. The concordance rate for NIDDM in monozygotic twins is >90%, and genetic factors appear to be the major determinants of its development.
NIDDM is a disorder in which hyperglycemia results from both an impaired insulin secretory response to glucose and decreased insulin effectiveness (insulin resistance).

The maximum acceptable plasma glucose levels are 80-120 mg/dL.
In treating IDDM, chronic insulin therapy is always required.
Insulin Preparations
Preparations of purified porcine insulin, purified bovine insulin, semisynthetic human insulin, and biosynthetic human insulin (all 99% pure, <10 parts per million [ppm] proinsulin) are now available; they have equivalent biologic activities.
Insulin is routinely provided in preparations containing 100 u./mL (U-100 insulin) and is injected s.c. with disposable insulin syringes calibrated for use with U-100 insulin, which are commercially available with maximal capacities of 100 u. (1 mL), 50 u. (0.5 mL), and 30 u. (0.3 mL).
Insulin Preparation
Onset of Action
Peak Action (h)
Duration of Action (h)
Rapid-acting regular
15-30 min
Rapid-acting Semilente® (insulin zinc suspension)
(prompt 1½-2 h
Intermediate-acting (NPH and Lente®)
1-3 h
Long-acting (Ultralente® and PZI)
4-8 h
NPH = neutral protamine Hagedorn; PZI = protamine zinc insulin.

Glucagon is a polypeptide hormone secreted by alpha cells, found almost exclusively in the pancreatic islets in humans. Glucagon is used to treat severe hypoglycemic reactions due to insulin;
Glucagon is available for injection in vials containing 1 u. (1 mg) or 10 u. (10 mg) of crystalline glucagon. The usual dose of glucagon in adults is 0.5 to 1 u. given s.c., IM, or IV; in children, it is 0.03 u./kg (maximum dose 1 u.). The major side effects are nausea and vomiting.

Immunologic insulin resistance
Occurs in patients receiving insulin longer than 6 months. In this case the dose of insulin should be increased and prednisone treatment initiated for decreasing of immune response.

Oral Hypoglycemic Agents
Oral hypoglycemic agents are in use in treatment of NIDDM.
Biguanides: metformin, phenformin
Effects: 1- decreasing glucose absorption in GIT; 2- inhibit glucagon secretion; 3- stimulation of tissue glycolysis.
Side effects: the major side effect is hypoglucemia; rarely metabolic acidosis may occur.
Sulfonureas: tolbutamide, chlorpropamide, acetohexamide, tolazamide, glyburide, glipizide.
Effects: 1- stimulating insulin secretion; 2- enhancing insulin action in target tissues.
Side effects: hypoglycemia, allergy, jaundice.

Vitamin A
Principal Sources: as preformed vitamin - fish liver oils, liver, egg yolk, butter, cream; as provitamin carotenoids: dark green vegetables, yellow fruits.
Functions: Photoreceptor mechanism of retina, integrity of epithelia, lysosome stability, glycoprotein synthesis.
Deficiency and Toxicity: deficiency - night blindness, hyperkeratosis, keratomalacia; toxicity – Headache, peeling of skin, hepato-splenomegaly, bone thickening.

Vitamin D
Principal Sources: ultraviolet irradiation, fish liver oils, milk, butter, egg yolk, liver.
Functions: Calcium and phosphorus absorption, mineralization and collagen maturation of bone; tubular reabsorption of phosphorus.
Deficiency and Toxicity: Primary - Rickets (tetany associated), osteomalacia, Metabolic – anorexia, renal failure.

Vitamin E group
Principal Sources: vegetable oil, wheat germ, egg yolk, margarine, vegetables.
Functions: Intracellular antioxidant, scavenger of free radicals.
Deficiency and Toxicity: neurologic damage, creatinuria, ceroid deposition in muscle, RBC hemolysis; toxicity - interferes with enzymes, increased infection.

Vitamin K - Vitamin K1 (phytonadione), Vitamin K2
Principal Sources: vegetables, pork, liver, vegetable oils, intestinal flora after newborn.
Functions: formation of prothrombin and other coagulation factors, normal blood period coagulation.
Deficiency and Toxicity: hemorrhage; toxicity – kernicterus

Essential fatty acids (linoleic, linolenic, arachidonic acids)
Principal Sources: vegetable seed oils (corn, sunflower)
Functions: precursors of prostaglandins, leukotrienes, various hydroxy fatty acids, membrane structure.
Deficiency and Toxicity: growth cessation, dermatosis.

Thiamine (vitamin B1)
Principal Sources: whole grains, meat, nuts, legumes, potatoes.
Functions: carbohydrate metabolism, central and peripheral nerve cell function, myocardial function.
Deficiency and Toxicity: Beri-beri - infantile and adult (peripheral neuropathy, cardiac failure); Wernicke-Korsakoff syndrome.

Riboflavin (vitamin B2)
Principal Sources: Milk, cheese, liver, meat, eggs.
Functions: Many aspects of energy and protein metabolism, integrity of mucous membranes.
Deficiency and Toxicity: angular stomatitis, corneal vascularization, amblyopia, sebaceous dermatosis.

Niacin (Vitamin B3)
Principal Sources: liver, meat, fish, legumes, whole-grain enriched cereal products.
Functions: Oxidation-reduction reactions, carbohydrate metabolism and CNS function.
Deficiency and Toxicity: Pellagra (dermatosis, glossitis, GI and CNS dysfunctions).

Vitamin B6 group (pyridoxine)
Principal Sources: liver, organ meats, fish, legumes.
Functions: many aspects of nitrogen metabolism - transaminations, porphyrin and heme synthesis, tryptophan conversion to niacin; linoleic acid metabolism.
Deficiency and Toxicity: convulsions in infancy, anemias, neuropathy, seborrhea-like skin lesions.

Folic acid
Principal Sources: fresh green leafy vegetables, fruit, organ meats, liver.
Functions: maturation of RBCs, synthesis of purines and pyrimidines.
Deficiency and Toxicity: pancytopenia; megaloblastosis (especially pregnancy, infancy, malabsorption).

Vitamin B12 (cobalamins)
Principal Sources: Liver, meats, fish, eggs, milk.
Functions: Maturation of RBCs; neural function; DNA synthesis, related to folate coenzymes; methionine and acetate synthesis.
Deficiency and Toxicity: Pernicious anemia, some psychiatric syndromes.

Principal Sources: Liver, kidney, egg yolk, cauliflower, nuts, legumes/
Functions: Carboxylation and decarboxylation of oxalocetic acid; amino acid and fatty acid metabolism.
Deficiency and Toxicity: dermatitis, glossitis.

Vitamin C (ascorbic acid)
Principal Sources: Citrus fruits, tomatoes, potatoes, cabbage, green peppers.
Functions: Essential to osteoid tissue, collagen formation, vascular function, wound healing.
Deficiency and Toxicity: Scurvy (hemorrhages, loose teeth, tissue gingivitis).

Principal Sources: wide distribution - beef, pork, sardines, cheese, green olives, corn bread, etc.
Functions: Acid-base balance, osmotic pressure, blood pH, muscle contractility, nerve transmission, sodium pumps.
Deficiency and Toxicity: hypo- and hypernatremia - confusion, coma.

Principal Sources: wide distribution - bananas, prunes, raisins, milk
Functions: muscle activity, nerve transmission; intracellular acid-base balance.
Deficiency and Toxicity: hypokalemia - paralysis, cardiac disturbances; hyperkalemia - paralysis, cardiac disturbances.

Principal Sources: Milk and milk products, meat, fish, eggs, cereal products, beans, fruits, vegetables.
Functions: bone and tooth formation, blood coagulation, neuromuscular irritability, muscle contractility, myocardial conduction.
Deficiency and Toxicity: hypocalcemia - neuromuscular hyperexcitability and tetany; hypercalcemia - GI atony, renal failure, psychosis.

Principal Sources: Milk, cheese, meat, fish, cereals, nuts, legumes.
Functions: Bone and tooth formation, acid-base balance, component of nucleic acids, energy production.
Deficiency and Toxicity: hypophosphatemia - weakness, blood cell disorders, GI tract and renal dysfunction, irritability; hyperphosphatemia - renal failure.

Principal Sources: green leaves, nuts, cereal grains, seafood.
Functions: bone and tooth formation, nerve conduction, muscle contraction, enzyme activation.
Deficiency and Toxicity: hypomagnesemia - neuromuscular irritability; hypermagnesemia – hypotension, respiratory failure, cardiac disturbances.

Principal Sources: wide distribution - soybean flour, beef, kidney, liver, beans, clams, peaches.
Functions: Hemoglobin, myoglobin formation, enzymes.
Deficiency and Toxicity: deficiency - anemia, dysphagia, enteropathy, decreased work performance, impaired learning ability; toxicity - hemochromatosis, cirrhosis, diabetes mellitus, skin pigmentation.

Principal Sources: Seafoods, iodized salt, dairy products.
Functions: Thyroxine (T4) and triiodothyronine (T3) formation and energy control.
Deficiency and Toxicity: deficiency – cretinism, fetal growth and brain development disorders; toxicity – thyrotoxicosis, myxedema.

Principal Sources: wide distribution--tea, coffee, fluoridation of water.
Functions: bone and tooth formation
Deficiency and Toxicity: deficiency - predisposition to dental caries, osteoporosis; toxicity - fluorosis, pitting of permanent teeth; exostoses of spine.

Principal Sources: wide distribution--vegetable sources.
Functions: component of enzymes and insulin; skin integrity, wound healing, growth.
Deficiency and Toxicity: growth retardation, hypogonadism, acrodermatitis enteropathica.

Principal Sources: wide distribution--organ meat, nuts, dried legumes, whole-grain cereals.
Functions: Enzyme component, hemopoesis, bone formation.
Deficiency and Toxicity: deficiency – anemia; toxicity - hepatolenticular degeneration, biliary cirrhosis.

Principal Sources: green leafy vegetables.
Functions: part of vitamin B12 molecule.
Deficiency and Toxicity: deficiency – anemia; toxicity – cardiomyopathy.

Principal Sources: wide distribution.
Functions: part of glucose tolerance factor.
Deficiency and Toxicity: impaired glucose tolerance.

Principal Sources: meats and other animal products.
Functions: component of glutathione peroxidase.
Deficiency and Toxicity: deficiency – cardiomyopathy; toxicity - loss of hair and nails, dermatitis, polyneuritis.

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