ENDOCRINE SYSTEM

Oxytocin
1. Stimulated by stretching of uterine cervix and sucking at nipple
2. Target organs: uterus: stimulates uterine contractions + initiates labor; breast - stimulates milk ejections
3. Hypo/hyper: UNKNOWN
Antidieuretic Hormone (ADH)
1. Increasing blood solute concentration/blood volume decreases; stimulates by pain, drugs, low bp. Inhibited by adequate hydration of the body + alcohol
2. Kidneys: to reabsorb water from forming urine in the blood
3. Hypo: diabetes insipidus
4. Hyper: syndrome of inappropriate ADH secretion
Follicle Stimulating Hormone (FSH)
1. Stimulated by GnRH, inhibited: feedback inhibition exerted by inhibin + estrogens (females) and testosterone (males)
2. Target organ: stimulates ovarian follicle maturation + production of estrogen
3. Testes: stimulates sperm production
4. Hypo: failure of sexual maturaiton
5. Hyper: no important effects
Luteinizing Hormone (LH)
1. Stimulated by GnRH; inhibited: feedback inhibition exerted by estrogens and progesterone in females and testosterone in males
2. Target organs: ovaries and testes: in females, triggers ovulation and stimulates ovarian production of estrogens and progesterone; males, promotes testosterone production
3. Hypo/hyper: as for FSH
Adrenocorticotropic hormone (ACTH)
1. Stimulated by release of CRH; stimuli increases CRH release includes fever, hypoglycemia, other stressors
2. Inhibitied: feedback inhibition exerted by glucocorticoids
3. Target: adrenal glands to release glucocorticoids and androgens
4. Hypo: rare
5. Hyper: cushing’s disease
Thyroid-stimulating hormone (TSH)
1. Stimulated by TRH + infants indirectly by cold temperature
2. Inhibited: thyroid hormone on anterior pituitary + hypothalamus
3. Target: thyroid gland: release thyroid hormones in thyroid gland
4. Hypo: myxedma
5. Hyper: similar to graves’ disease
Prolactin
1. Sitmulated by decreased PIH, relase enhanced by estrogens, BCP, breast–feeding, and dopmaine-blocking drugs; inhibited by PIH (dopamine)
2. Breast secretory tissue: promotes lactation
3. Hypo: poor milk production in nursing women
4. Hyper: inappropriate milk production (galactorrhea); cessation of menses in females; impotence in males
Growth Hormone (GH)
1. Release of GH, low blood levels of fatty acids, low blood levels of GH, high blood levels of amino acids, deep sleep, exercise, hypoglycemia, and other stressors
2. Inhibited by GH + insulin-like growth factors (IGFs), hyperglycemia, hyperlipidemia, obesity, emotional deprivation driven by high GHIH and low GHRH
3. Target organs: liver, muscle, bone, cartilage: anabolic tissue, stimulates somatic growth, mobilizes fat, spares glucose, and growth-promoting effects mediated indirectly by IGFs

Hormones proudced by Organs Other than the Major Endocrine ORgans

Leptin (adipose)
1. Secretion proportional to fat stores; increased by nutrient uptake
2. brain : suppresses appetite; increases energy expenditure
Resistin, (adipose)
1. Secretion proportional to fat stores for resistin, inversely proportional for adiponectin
2. Fat, muscle, liver, resistin antagonizes, insulin’s action and adiponectin enhances it
GI tract mucosa
1. Gastrin/ ghrelin (stomach)
  1. Increases HCI secretion • Stimulates gastric emptying (minor effect) • Stimulates contraction of intestinal muscle • Relaxes ileocecal valve • Stimulates mass movements
2. Secretin/ cholecystokinin, glucose-dependent insulinotropic peptide
  1. • Inhibits gastric gland secretion and gastric motility • Increases output of pancreatic juice rich in bicarbonate ions; potentiates CCK's action • Increases bile output
Atrial natriuretic peptide (ANP) (heart)
1. Secreted in response to stretching of atria
2. Kideney; inhibits sodium ion reabsorption and renin release
3. Adrenal cortex: inhibits secretion of aldosterone; decreases BP
Erythropoietin (EPO) (kidney)
1. Secreted in response to hypoxia
2. Red bone marrow: stimulates production of RBCs
Osteocalcin (skeleton)
1. Increases insulin production and insulin sensitivity
Cholecalciferol – Skin (epidermal cells)
1. Activated by the kidneys to active vitamin D3, in response to parathyroid hormone
2. Intestine; stimulates active transport of dietary calcium across cell membranes of small intestine
Thymulin,- thymus
1. Unknown
2. Mostly act locally as paracrines, involved in T lymphocyte development and in immune responses

Adrenal Gland Hormones
1. Mineralocoritoids
  1. Stimulated by renin-angiotensinaldosterone mechanism (decreasing blood volume or blood pressure), elevated blood K+ levels, and ACTH. Inhibited by increased blood volume and pressure, and decreased K+ blood ldevels
  2. Kidneys; increase blood levels of Na+ and decrease blood levels of K+, water reabsorption is usually accomapnies sodium retention, blood volume and blood pressure rise
  3. Hypo: aldosteronism
  4. Hyper: addison’s disease
2. Glucocorticoids -
  1. Stimulated by ACTH, inhibited by feedback inhibition exerted by cortisol
  2. Body cells; promote glucoeogenesis and hyperglycemia; mobilize fats for energy metabolism; stimulate protein catabolism; assist body to resist stressors, depress inflamatory and immune responses
  3. Hypo: addision’s
  4. Hyper: cushing’s syndrome
3. Gonadocorticoids -
  1. Stimulated by ACTH, inhibition understood, but inhibition not seen
  2. Insignificant effects in males; contributes to female libido; development of public and axillary hair in females; source of estrogens after menopause
  3. Hyper: masculinization of females
  4. Hypo: no effects known

Andrenal medullary hormones

Catecholamines
1. Stimulated by preganglionic fibers of sympathetic nervous system
2. Sympathetic nervous system target organs: effects mimic sympathetic nervous system activation; increase heart rate and metabolic rate; increase blood pressure by promoting vasoconstrction
3. Hyper: prolonged fight-or-flight response; hypertension
4. Hypo: unimportant

Clinical Cases

Diabetes insipidus - syndrome marked by intense thirst and huge urine output (diabetes = overflow; insipidus = tasteless) distinguishes it from diabetes mellitus (mel = honey), in which insulin deficiency causes large amounts of blood glucose to be lost in the urine.
- Can be caused by a pituitary tumor or by a blow to the head that damages the hypothalamus or the posterior pituitary. Not serious when the thirst center is operating properly and the person drinks enough water to prevent dehydration. However, it can be life threatening in unconscious or comatose patients, so accident victims with head trauma must be carefully monitored
- Syndrome of inappropriate ADH Secretion (SIDAH) Opposite problem– hypersecretion of ADH– occur in children with meningitis, or adults who have neurosurgery, hypothalamic injury, or cancer in which cancer cells are additional sources of ADH. May occur after general anesthesia
  - retention of fluid,
  - headache and disorientation due to brain edema
  - Weight gain
  - Decrease solute concentration in the blood
  - Management: restricting fluids and carefully monitoring

Gigantism - hypersection in children, GH targets the still-active epiphyseal (growth) plates.
- Person becomes abnormally tall, often reaching a height of 2.4 m (8 feet), but has relatively normal body proportions
Acromegaly - occurs when excessive GH is secreted after the epiphyseal plates have close
- “Enlarged extremities”
- Overgrowth of bones of the hands, feet, and face
- Hypersection results from an anterior pituitary tumor that churns out excessive GH. The usual treatment is surgical removal of the tumor, but this surgery does not reverse anatomical changes that have already occurred.
Pituitary dwarfism - hyposecretion of GH in adults usually causes no problems, but GH deficiency in children slows long bone growth
- Such individuals attain a maximum height of 1.2 m (4ft), but usually have fairly normal body proportions. Lack of GH is often accompanied by deficiencies of other anterior pituitary hormones, and if thyroid-stimulating hormone and gonadotropins are lacking, the individual will be malproportioned and will fail to mature sexually
Availability of synthetic GH also has a downside. Athletes and the elderly have been tempted to use GH for its body-building properties, and some parents seek to give their children the hormone to make them taller
Hyperprolactinemia - hypersecretion of prolactin; most frequent abnormality of anterior pituitary tumors
- Clinical signs: inappropriate lactation, lack of menses, infertility in females, and impotence in males
Hangover
- Drinking alcoholic beverages inhibits ADH secretion and causes copious urine output. The dry mouth and intense thirst of a “hangover” reflect this dehydrating effect. Drinking lots of water inhibits ADH release
Hypothyroid disorder - results from some thyroid gland defects or secondarily from inadequate TSH or TRH release. Also occurs when the thyroid gland is removed surgically and when dietary iodine is inadequate.
Myxedema - “mucous swelling”, adult full-blown hypothyroid syndrome
- Low metabolic rate
- Feeling chilled
- Constipation
- Thick , dry skin
- Puffy eyes
- Edma
- Lethargy
- Mental sluggishness
Goiter - enlarged protruding thyroid gland, occurs if myxedema results from lack of iodine
- Follicular cells produce colloid but cannot iodinate it and make functional hormones.
- Pituitary gland secretes increasing TSH in an attempt to stimulate the thyroid to produce TH, but the only result is that the follicles accumulate more and more unusable colloid. Depending on the cause, iodine supplements or hormone replacement therapy can reverse myxedema
- Goiter, iodine-poor soil, no access to iodine-rich seafood.
Congenital hypothyroidism - usually caused by poor development of the thyroid gland
- In the first weeks of life, an infant with congenital hypothyroidism may have no symptoms at all, or may present with a weak cry, poor feeding, constipation, or prolonged jaundice
- Early treatment: oral thyroid hormone replacement is crucial and usually allows a normal, healthy life.
Graves’ disease - autoimmune condition, a person makes abnormal antibodies directed against thyroid follicular cells. Antibodies paradoxically mimic TSH and continuously stimulate TH release
- Symptoms
  - Elevated metabolic rate
  - Sweating
  - Rapid, irregular heartbeat
  - Nervousness
  - Weight loss despite adequate food
  - Eyeball protrusion if tissue behind eyes become edematous and fibrous
- Treatment: surgical removal of thyroid gland/ingesting radioactive iodine which destroys the most active thyroid cells.
Calcitonin
- Polypeptide hormone released by the parafollicular (C cells) in response to a rise in blood Ca2+ levels
- Does not need to be replaced in patients who thyroid gland has been removed
- Pharmacological disease has bone-sparing effect and is given therapeutically to treat Paget’s disease and sometimes osteoporosis
- Targets the skeleton where it:
  - Inhibits osteoclast activity
  - Inhibiting bone resorption and release of Ca2+ from the bony matrix
  - Stimulates Ca2+ uptake and incorporation into bone matrix
Hyperparathyroidism - caused by parathyroid gland tumor. Calcium leaches from the bones, which soften and deform as fibrous cystica (severe form of disorder) – moth eaten-appearance on x-rays and tend to fracture spontaneously. The resulting hypercalcemia (abnormally elevated blood Ca2+ level) has many outcomes, but the two most notable are 1) depresses the NS and 2) excess calcium salts precipitate in the kidney tubules, forming kidney stones.
Hypoparathyroidism (PTH deficiency) - most often follows parathyroid gland trauma or removal during thyroid surgery. The resulting hypocalcemia (low blood Ca2+) makes neurons more excitable and accounts for the classic signs and symptoms of tingling sensations, tetany (twitching muscle), and convulsions.
Aldosteronism - typically results from adrenal tumors
- Two major sets of problems
  - hypertension and edema due to excessive Na+ and water retention
  - Accelerated excretion of potassium ions. If K+ loss is extreme, neurons become nonresponsive, leading to muscle weakness and eventually paralysis
Cushing’s syndrome
- ACTH-releasing pituitary tumor by an ACTH-releasing malignancy of the lungs, pancreas, or kidneys; or by a tumor of the adrenal cortex.
- Persistent elevated blood glucose levels
- Losses in muscle and bone protein
- Water and salt retention
- Hypertension and edema
- Signs: swollen “moon” face, redistribution of fat to the abdomen and the posterior neck (buffalo hump), easy brusiing, poor wound healing. Infections may become overwhelmingly severe before producing recognizable symptoms. Muscles weaken + spontaneous fractures force the person to be bedridden
Addison’s disease
- Major hyposecretory disorder of the adrenal cortex, usually involves deficits in both glucocorticoids and mineralocorticoids: plasma glucose and sodium levels drop and potassium levels rise. Severe dehydration and hypotension are common. Corticosteroid replacement therpy is the usual treatment
- Common early sign: bronzing of skin (lack of negative feedback by corticosteroids increases ACTH release by the anterior pituitary. At high levels, ACTH triggers melanin production in melanocytes)
Adrenogenital Syndrome (masculinization) - hypersecretion of gonadocorticoids

Adult males, elevated gonadocorticoid levels. Prepubertal males. In boys, reproductive organs mature and secondary sex characteristics appear early, and the sex drive emerges with a vengeance. Females develop a beard and a masculine distribution of body hair, and the clitoris grows to resemble a small penis.

Pheochromocytoma - hypersecretion of catecholamines, sometimes arising from a medullary chromaffin cell tumor. Produces symptoms of uncontrolled sympathetic nervous sytem activity – increased metabolic rate, rapid heartbeat and palpitations, hypertension, intense nervousness, and sweating.

Prolactjnoma - The most common type (30-40% or more) of pituitary gland tumor; evidenced by hypersecretion of prolactin and menstrual disturbances in women.
Thyroid storm (thyroid crisis) - A sudden and dangerous increase in all of the manifestations of hyperthyroidism due to excessive amounts of circulating TH. Signs include fever, rapid heart rate, high blood pressure, dehydration, nervousness, and tremors. Precipitating factors include severe infection, excessive intake of TH supplement~. or trauma.
Galactorrhea Inappropriate lactation ( discharge of milk from the nipple). May occur in women who are not breastfeeding, and in men. Usually due to excess prolactin.
Hirsutism - (hairy, rough) Excessive hair growth; usually refers to this phenomenon in women and reflecL~ excessive androgen production.
Hypophysectomy - Surgical removal of the pituitary gland

Diabetes mellitus (DM) - hyposecretion or hypoactivity of insulin

Type 1- insulin absent

Type 2 - insulin present, but deficient effects

Polyuria - hugh urine output that decreases blood volume and causes dehydration

Polydipsia - dehydration stimulates hypothalamic thirst centers, causing polydipsia

Polyphagia - excessive hunger and food consumption, a sign that the person is “starving in the land of plenty”

Knowt