Endocrinology

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1

endocrinology

study of hormones and disorders of these hormones

2

endocrine system

hypothalamus and pituitary, thyroid and parathyroid, kidney, adrenals, gonads: ovaries and testicles, and Islets of Langerhans

3

hormone

any substance normally produced by specialized cells in some part of the body, carried by the blood stream to another part, where it effects the body as a whole; vehicles for intracellular and extracellular communication

4

hormone characteristics

specificity, multiple actions, variable forms, excretion rates

5

specificity

hormones only target specific cells for response

6

variable half-life

dependent on the weight of the hormone

7

excretion rates

diurnal variation, cyclic patterns, and stimulus response of hormone

8

hormone functions

maintain homeostasis, regulate growth and development, promote sexual maturation, sexual rhythms and facilitate reproduction, regulate energy production, adapt and adjust body to stressful and emergency situations, and promote and inhibit production or release or other hormones

9

peptides and proteins

polypeptides or glycoproteins, soluble in plasma, interact with target cell membrane receptors to trigger a second messenger to complete the specific action of the hormone; short term effects

10

amines

amino acid derivatives, poorly soluble in plasma, interact with membrane receptors of target cells, and provide long and short term effects

11

steroids

composed of lipids (cholesterol), can transverse through the cell membrane; produced by ovaries, testis, placenta, and adrenal cortex; insoluble in water; long-lasting

12

tropic

originate from anterior pituitary gland; specific for another endocrine gland

13

non-tropic or direct effector

secreted by non-pituitary endocrine glands; act directly on peripheral tissue; exert a feedback effect on the hypothalamus or anterior pituitary gland

14

hormone receptors

located on cell membrane or within cell cytoplasm; binding of hormone to receptor initiates a signal; results in changes in gene expression; ultimately causes a biological response

15

negative feedback control

an increase in the product causes a decrease in the system; serves to stabilize a process; primary means of hormone regulation

16

positive feedback control

an increase in the product causes an increase in the activity of the system

17

regulation and control

occurs by controlling the rate of synthesis rather than the rate of degradation

18

hypothalamus

the primary control; small gland next to pituitary gland connected to the pituitary by the pituitary stalk

19

pituitary gland

releases both tropic and effector hormones

20

thyrotropin releasing hormone

releases TSH and prolactin

21

gonadotropin releasing hormone

releases LH and FSH

22

corticotropin releasing hormone

releases ACTH

23

growth hormone releasing hormone

releases GH

24

somatostatin

inhibits GH and TSH release

25

dopamine

inhibits prolactin release

26

oxytocin

promotes uterine contraction and milk let down released in posterior pituitary

27

anti-diuretic hormone

affects water volume

28

anterior pituitary (adenohypophysis)

hormones which target other endocrine glands; forms the lactotrophs, somatotropin, throtrophs, corticotrophins and gonadotrophs

29

intermediate lobe (pars intermedialis)

little functional capacity

30

posterior pituitary (neurohypophysis)

stores and releases oxytocin and vasopressin (ADH)

31

luteinizing hormone (LH)

targets gonads: ovaries, testes; tropic; sex steroid feedback; regulates ovulation, testosterone production

32

follicle stimulating hormone (FSH)

targets ovary; tropic; inhibin feedback; regulates ovarian recruitment

33

thyroid stimulating hormone (TSH)

targets thyroid; tropic; thyroid hormone feedback (T4/T3); stimulates thyroid hormone production

34

adrenocorticotropin hormone (ACTH)

targets adrenal cortex; tropic; cortisol feedback; stimulates synthesis and secretion of glucocorticoid hormones

35

growth hormone (somatotropin)

targets multiple glands; peptide with direct effector; insulin-like growth factor feedback; stimulates tissue growth; amphibolic

36

prolactin

targets breasts; direct effector; unknown feedback hormone; functions in secretion

37

amphibolic

influences both anabolic and catabolic processes

38

growth hormone

allows effective transition from fed to fasting state without substrate shortage; directly antagonizes insulin effects on glucose metabolism; provides hepatic gluconeogenesis; stimulates lipolysis; enhances protein synthesis in skeletal muscle and other tissues; stimulates production of insulin-like growth factors

39

growth hormone stimulators

meals, exercise, sleep, and hypoglycemia

40

growth hormone inhibitors

glucose loading, epinephrine, emotional and psychogenic stress, nutritional deficiencies, and insulin deficiency

41

growth hormone testing

based on dynamic physiology of growth hormone axis; testing for autonomous production of growth hormone relies on normal suppression of growth hormone by oral glucose loading

42

GH stimulation

insulin-induced hypoglycemia (outdated method); combination infusions of GHRH and amino acid L-arginine; infusion of L-arginine coupled with oral L-DOPA

43

acromegaly

results from pathologic or autonomous growth hormone excess; usually caused by a pituitary tumor; causes gigantism, bony and soft tissue overgrowth, progressive enlargement of hands, feet, mandible, and skill, arthritis, diabetes, hypertension, atherosclerosis, muscle weakness, sleep apnea, and shortened life expectancy; greater risk of developing cancer

44

growth hormone deficiency

occurs in both children and adults; genetic or tumor caused with growth failure in children or result of structural or functional pituitary abnormalities in adults; recessive mutation in GHRH gene, failure of GH secretion, loss of GH gene, GH insensitivity, and structural lesions of pituitary or hypothalamus

45

prolactin

functions in relation to reproduction, breast growth during pregnancy, milk secretion, direct effector, stimulated by thyrotropin-releasing hormone; inhibited by dopamine

46

posterior pituitary

does not synthesize hormones; stores and releases hormones made by the hypothalamus to be transported along the hypothalamohypophyseal tract; oxytocin and antidiuretic hormone or vasopressin

47

oxytocin

released from posterior pituitaryfunctions in lactation stimulating milk let down and stimulating smooth muscle in the uterus; synthetic is Pitocin used to induce or enhance labor contractions

48

ADH/ vasopressin

regulates water excretion in the renal tubules where the receptors are found; assists in water balance; hypothalamic osmoreceptors and vascular basoceptors regulate release from posterior pituitary

49

ADH deficiency

hormone imbalance of diabetes insipidus with symptoms of >2.5L per day urinary output, excessive thirst, and dehydration

50

water deprivation test

monitors ADH and urine osmolality levels

51

syndrome of inappropriate antidiuretic hormone secretion (SIADH)

increased ADH with low plasma osmolality levels; urine Na increases, plasma Na decreases

52

hypopituitarism

failure of either pituitary or hypothalamus results in loss of anterior pituitary function; associated with low or normal levels of tropic hormone; both tropic and target hormone levels should be measured under suspicion of pituitary failure; if one secondary deficiency is documented, other deficiency states and cause of pituitary failure must be found

53

panhypopituitarism

complete loss of function

54

mono tropic hormone deficiency

loss of only a single hormone

55

endocrinology

study of intracellular and extracellular communication by messenger molecules known as hormones

56

paracrine

hormone that acts on neighboring cells-don't travel far

57

autocrine

hormone that acts on cells in which it was produced

58

endocrine

message sent through circulation to a distant cell

59

hypothalamus, thyroid, parathyroid, stomach, spleen, adrenal, liver, duodenum (intestines), pancreas, kidney cortex

10 endocrine glands

60

steroids

hydrophobic-bound to transport proteins; 30-100 minute half-life

61

glucocorticoids, mineralcorticoids, androgens, estrogens, progesterens

5 steroid hormones

62

polypeptides or proteins

water-soluble, circulate unbound, rapid fluctuations; 10-30 minute half-life

63

growth hormones, follicle-stimulating hormone, anti-diuretic hormone

3 polypeptide hormones

64

regulatory, growth and development, integrative action

3 main hormone actions

65

intracellular and extracellular fluid composition, regulate salt, water, carbohydrate, fat, and protein metabolism, responds to starvation, infection, trauma, physiological stress, and sexual reproduction

regulatory functions of hormones

66

growth and development

morphogenesis hormone actions

67

carb metabolism, cortisol

integrative action of hormones

68

anterior pituitary gland

adenohypophysis

69

anterior pituitary gland

central position in control of hormone secretion; produces (tropic) hormones that target other endocrine glands to secrete additional hormones

70

thyroid, adrenal cortex, gonads

main targets of anterior pituitary gland

71

positive feedback

increase in product increases the activity of the system, which increases the rate of production of the product

72

synthesis of LH

positive feedback example

73

negative feedback

increase in the product decreases the activity of the system, resulting in a decrease of the product

74

adrenocortical, gonadal, and thyroid

examples of negative feedback

75

CNS

controls the posterior pituitary gland (neurohypophysis) and adrenal medulla

76

neurohypophysis

vasopressin, oxytocin

77

adrenal medulla

epinephrine

78

hypothalamus-hypophyseal system

variable-feedback control system-positive or negative

79

biorythms

cyclical occurrence of a physiological event

80

circadian (diurnal)

light/dark or sleep cycle

81

ultradian

time periods more than once a day

82

infradian

time periods longer than 24 hours

83

every 90 minutes

LH biorythms

84

peak at 8am; lowest at midnight

ACTH biorythms

85

highest before midnight; surges during REM

TSH biorythms

86

hormone receptors

provides target cell with a mechanism for recognizing and concentrating the hormone

87

hormone-receptor complex

activates target cell to begin chain of events; highly specific (only by acting free hormone)

88

highly specific, equilibrium system, saturable, and high affinity

four characteristics of hormone/receptor complex

89

peptide hormones and catecholamines

bind to receptors on or in cell membrane

90

G-protein and protein kinases

peptide hormone and catecholamine receptors

91

steroids and thyroid hormones

target organ cells; bind with intracellular receptors, not on surface since they are mostly lipid soluble hormones

92

excess or deficiency, abnormal hormone produced, resistance of hormone action, abnormalities of hormone action, abnormalities of hormone transport or metabolism, and multiple endocrine abnormalities

six classes of endocrine disorders

93

bioassays

based on observations of physiological responses specific for the hormone being measured; difficult, ingestion of materials, in vitro-cell culture

94

receptor assay

in vitro interaction of a hormone with its biological receptor; simpler

95

immunoassays

used to quantitate hormones, but does not give information as to the function

96

pituitary

spit mucous; brain directs gland to secrete hormones to impact other glands; master gland that impacts growth and many other functions; transponder that interprets and acts on brain signal

97

hypophysis (pituitary gland)

under the hypothalamus

98

feedback loops, pulsatile secretions, diurnal rhythms, and environmental/external modification of performance

four features of the pituitary gland

99

adenohypophysis

anterior pituitary

100

intermediate lobe

portion of pituitary that is poorly developed in humans and has limited functional use

101

neurohypophysis

posterior pituitary gland

102

7-9 weeks gestation

gestational development of pituitary gland

103

TSH, ACTH, LH, FSH, GH, and prolactin

6 anterior pituitary hormones

104

oxytocin, vasopressin

2 posterior pituitary hormones

105

hypothalamic-hypophyseal portal system

how arterial and venous blood reach the pituitary gland

106

venous blood

carries the neurosecretory hormones from the hypothalamus

107

hypothalamic hormones

stimulate or inhibit hormone release from adenohypohpysis

108

neural modulation

regulates anterior pituitary hormone pulsatile frequency

109

cyclic nature

external signals (night/day) pituitary cycle

110

hypothalamus

manufactures small peptides, releasing or inhibiting factors produce effects on pituitary gland

111

SS

inhibits GH and TSH

112

TRH

stimulates secretion of TSH and prolactin

113

GnRH

stimulates LH and FSH

114

CRH and ADH

stimulates ACTH

115

Table 20.1

x

116

growth hormone, prolactin, thyrotropin, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone

anterior pituitary hormones

117

direct effector vs tropic

table 20.2

118

silent pituitary adenoma

pituitary tumor that occurs in approximately 20% of the population

119

prolactin-secreting

most common pituitary tumor

120

null cell tumors and tumors secreting GH, gonadotropin, ACTH, and TSH

pituitary tumor types

121

growth hormone

direct effector essential for growth; stimulated by releasing hormone by pituitary; inhibited by SS; secreted in pulses every 2-3 hours; open loop of stimulation by exercise, physical and emotional stress, hypoglycemia, increased AA levels, testosterone, estrogen, thyroxine

122

somatotropin

other name for growth hormone

123

table 20.3

x

124

amphibolic hormone

influences anabolic and catabolic processes

125

growth hormone

amphibolic hormone

126

effective transition from fed state to fasting state

major effect of growth hormone

127

antagonizes insulin effect, promotes hepatic gluconeogenesis, and stimulates lipolysis

three minor effects of growth hormone

128

enhanced protein synthesis in skeletal muscle and other tissues

anabolic effects of growth hormone

129

insulin-like growth factors

induced by GH; somatomedins; promotes growth and development; structurally and biologically similar to insulin but different receptors; can interact with insulin receptor causing hypoglycemia; amplifies GH levels; associated with some cancers

130

IGF

levels often associated with GH levels

131

autonomous testing

growth hormone testing based on normal suppressibility of growth hormone by oral glucose loading (100 g) then measuring fasting, 60minute, and 120 minute; undetectable in normal, detectable in acromegaly

132

deficiency testing

gold standard insulin-induced hypoglycemia for growth hormone testing; more complicated method

133

GHRH and arginine

stimulating GH hormone by infusing into patients; normal patients, levels detectable

134

acromegaly

pathologic or autonomous GH excess; often due to pituitary tumor, ectopic GHRH production, genetic mutation; leads to gigantism, bony and soft tissue overgrowth, glucose intolerance or diabetes, hypertension, atherosclerosis, muscle weakness, organomegaly; shortened life span, increased cancer risk

135

40% prolactin

cosecreted hormone in acromegaly

136

growth hormone deficiency

genetic or tumor related in children, structural or functional pituitary abnormalities; associated with osteoporosis and reduced body mass

137

PRL

prolactin

138

prolactin (PRL)

structurally similar to GH and human placental lactogen; stress hormone involved in reproduction; regulation and control; low levels midday, highest shortly after deep sleep onset

139

dopamine

prolactin inhibitory factor

140

PRF

TRH, estrogens, and suckling-lactation

141

lactation

physiological effect of prolactin

142

renal failure and polycystic ovary syndrome

seen with elevated levels of prolactin

143

initiation and maintenance of lactation, effects on immune system, impt in osmolality control and some metabolic events, fetal lung development, and steroidgenesis

5 functions of PRL

144

prolactinoma

pituitary tumor caused by abnormal prolactin levels

145

hypopituitarism

failure of pituitary or hypothalamus; loss of anterior pituitary function

146

panyhpopituitarism

complete loss of hypopituitary

147

monotropic hormone deficiency

loss of a single pituitary hormone

148

loss of tropic hormone

cessation on affected endocrine gland due to hypopituitarism

149

loss of direct effector

not always readily apparent form of hypopituitarism

150

pituitary tumors, infection, parapituitary or hypothalamic tumors, infiltrative disease, trauma, immunologic, trauma, radiation therapy, infarction, familial, and idiopathic

10 causes of hypopituitarism

151

oxytocin

has roles in lactation and labor; effects in pituitary, renal, cardiac and immune function

152

vasopressin

another name for antidiuretic hormone

153

antidiuretic hormone (vasopressin)

major function is water balance; regulates free water excretion; osmolality of blood is predominant regulator through receptors in the hypothalamus responding, causing thirst and kidney coordination; can respond to other stimuli: pain, stress, exercise, angiotensin II, catecholamines, anesthetics, and opiates; inhibited by increased plasma volume, decreased plasma osmolality, alcohol, and glucocorticoids

154

polyuric state

failure of renal tubules to reabsorb solute-free water due to hypofunction of ADH

155

hypothalamic diabetes insipidus

failure of pituitary gland to secrete normal amounts of ADH in response to osmoregulatory factors

156

nephrogenic diabetes insipidus

failure of kidneys to respond to normal or increased ADH

157

psychogenic or primary polydipsia

chronic, excessive intake of water suppresses ADH and produces hypotonic urine

158

syndrome of inappropriate antidiuretic hormone secretion (SIADH)

autonomous, sustained production of ADH in the absence of known stimuli for its release; levels are inappropriately increased relative to low plasma osmolality and normal or increased plasma volume; caused by malignancy, CNS disease, pulmonary disorders, drug therapy side effect; should be differentiated from CHF, renal insufficiency, nephrotic syndrome, liver cirrhosis, and hypothyroidism

159

thyroid gland

located in lower neck; two lobes on either side of the trachea attached at the isthmus

160

thyroid follicle

secretory unit of the thyroid gland; composed of outer layer of epithelial cells that enclose an amorphous material (colloid)

161

colloid

made up of thyroglobulin and iodinated thyroalbumin

162

parathyroid glands

four glands located underneath thyroid glands that play an important role in calcium balance

163

parafollicular C cells

part of the parathyroid gland that secrete calcitonin

164

iodine

the primary component of the thyroid hormone

165

production and accumulation of the raw materials

thyroid hormone synthesis step 1

166

fabrication or synthesis of the hormones on a backbone or scaffold of precursor

thyroid hormone synthesis step 2

167

release of the free hormones from the scaffold and secretion into the blood

thyroid hormone synthesis step 3

168

tyrosine

found in the colloid made by thryoid epithelial cells secreted into the lumen of the follicle; a pool of thyroglobulin

169

134

amount of tyrosines contained within one molecule of thyroglobulin; used to make T3 and T4

170

monoiodothyronine

MIT

171

diiodothyronine

DIT

172

thyroid peroxidase (TPO)

integral membrane protein present on colloid facing plasma membrane; has the ability to catalyze two important reactions

173

catalyzes iodination of tyrosines on thyroglobulin and produces MIT and DIT; synthesizes T3 (triiodothyronine) and T4 (thyroxine)

two functions of TPO

174

1 MIT and 1 DIT

triiodothyronine hormone molecules

175

2 DIT

thyroxine hormone molecules

176

thyroxine-binding globulins TBG, thyroxine-binding preablumin (TPBA), and albumin

the three major binding proteins for thyroid hormone

177

thyroid stimulating hormone

released from anterior pituitary gland; binding to receptors stimulates synthesis of iodine transporter, thyroid peroxidase, and thyroglobulin; magnitude of signal increases endocytosis rates

178

tissue growth, brain maturation, increased heat production, increased oxygen consumption, increased Beta-adrenergic receptors

5 actions of thyroid hormone

179

increased metabolic activity

effect of increased thyroid hormone

180

decreased metabolic activity

effect of decreased thyroid hormone

181

do not exclude disease

normal thyroid hormone levels

182

do not always indicate thyroid disease

abnormal thyroid hormone levels

183

TSH

most useful test for thyroid evaluation

184

serum T4 and T3

RIA, chemi or immuno; total levels aren't usually very useful due to protein changes; measure free

185

thyroglobulin

thyroid follicular cells, thyroid cancer tumor marker, measured through RIA, ELISA, chemi-

186

thyroid autoimmunity

anti-TSH, antithyroglobulin, and anti-TPO

187

TSH testing

reflects integrative action of thyroid hormone in one of its target tissues; pituitary cells that secrete; third generation widely used

188

all generations

testing method primary hypothyroidism

189

2nd generation

screen for hyperthyroidism through immunoassay

190

3rd generation

most commonly used TSH testing generation; increased sensitivity; reduces false negatives; through chemiluminometric; distinguish between euthyroidism and hyperthyroidism; allows for designation of subclinical disease

191

4th generation

research use for TSH testing

192

free T4, T3 if free T4 is normal

Next steps: undetectable TSH and hyperthyroid suspect

193

free T4, T3, possibly TRH

next steps: subnormal TSH, borderline thyroid status

194

no further thyroid tests

next steps: normal TSH, no thyroid dysfunction

195

free T4

next steps: elevated TSH, hypothyroid suspect

196

bound to binding proteins; free hormone is the active hormone

limitation of T3 and T4 measurement

197

thyroglobulin

stored in follicular colloid of the thyroid gland; measurement is evidence of thyroid tissue

198

thyroglobulin tumor marker

elevated in thyroid follicular and papillary carcinoma, thyroid adenoma. subacute thyroiditis, Hashimoto's thyroiditis, Graves' disease

199

autoantibodies

impact measurement of thyroglobulins

200

thyroid autoantibodies

found in variety of thyroid disorders, some autoimmune diseases and malignancies; directed against thyroid and thyroid hormone antigens with different impacts

201

TSH receptor antibodies

seen in Graves' disease; stimulates receptor; growth of thyroid gland; excess thyroid hormone; tests to detect TSH receptor antibodies; thyroid stimulating immunoglobulins stimulate thyroid gland

202

antithyroglobulin antibodies

present in 85% of Hashimoto's thyroiditis and 30% of Graves' disease

203

anti-thyroid peroxidase

Hashimoto's thyroiditis, idiopathic myxedema, and majority of Graves' disease; occasionally detectable in normal individuals, especially elderly

204

nuclear medicine evaluation

radioactive iodine assesses metabolic activity of thyroid tissue; radioactive iodine uptake

205

thyroid ultrasound

used to identify thyroid nodules

206

fine needle aspiration

identifies thyroid malignancies

207

hypothyroidism, thyrotoxicosis, Graves' disease, and toxic adenomas and multinodular goiter

four groupings of thyroid disorders

208

drug-induced thyroid dysfunction

amiodarone-induced thyroid disease; subacture thyroiditis

209

hypothyroidism

characterized by low free T4 and normal to high TSH; one of the most common disorders of the thyroid gland; cold intolerance, fatigue, dry skin, weight gain, low body temp, slow movements, bradycardia, yellow coloring, hair loss, menstrual irregularities; inappropriate ADH leading to hyponatremia, myopathy and high CK, anemia, and hyperlipidemia

210

chronic lymphocytic thyroiditis (Hashimoto's), thyroidectomy (toxic goiter), radioactive iodine uptake, and subacute thyroiditis

four primary thyroid gland dysfunctions

211

primary thyroid gland dysfunction

the thyroid gland itself is affected

212

secondary pituitary dysfunction

patient has hypthyroidism at the pituitary level

213

tertiary hypothalamic dysfunction

patient has hypothyroidism at the hypothalamic level

214

hypopituitarism

secondary pituitary dysfunctin

215

hypothalamic dysfunction

tertiary pituitary dysfunction

216

levothyroxine (T4)

hypothyroidism treatment to achieve normal TSH level

217

myxedema

extreme low level of thyroid hormone; undiagnosed or untreated hypothyroidism; characterized by swelling of skin and other tissues (eyes and cheeks); can be congenital

218

thyrotoxicosis

hyperthyroidism conditions; peripheral tissue respond to excess thyroid hormone; excess free T4 and T3 which suppresses production of TSH (can be increased when pituitary tumor is present); caused by hyperfunction of thyroid, excessive leakage from nonhyperactive gland, sources other than thyroid, and excessive thyroid hormone ingestion); symptoms include anxiety, weakness, tremor, palpitations, heat intolerance, increased perspiration

219

Graves' disease

most common cause of thyrotoxicosis; antibodies are produced which activates TSH receptor; symptoms include thyrotoxicosis, goiter, opthalmopathy (eye changes), dermopathy; high free T4 and T3 with undetectable TSH; increased RAIU; treated with medication, radioactive iodide, surgery

220

toxic adenomas and multinodular goiters

relatively common causes of hyperthyroidism; thyroid tissue is autonomous in function without presence of TSH or TSHR-stimulating immunoglobulin; may be due to genetic mutation; adenomas have highly increased RAIU

221

drug-induced thyroid dysfunction

amiodarone-induced thyroid disease; cardiac drug that contains a large amount of iodine and results in inhibiting thyroid hormone production; Wolff-Chaikoff effect; inhibits T4 and T3 as well; leads to inflammation of thyroid gland leading to leakage of stored thyroid hormone; can also occur with large doses of iodine which acutely inhibits TH production

222

subacute thyroiditis

transient changes in levels; thyrotoxic phase with TH leakage, hypothyroid repair phase, then euthyroid phase after repair

223

postpartum thyroiditis

most common subacute thyroiditis; 3-16% of postpartum women; strongly associated with TPO antibodies and chronic lymphocytic thyroiditis

224

subacute granulomatous

subacute nonsuppurative thyroiditis or de Quervain's thyroiditis; ESR and thyroglobulin increased

225

23.4

...

226

nonthyroidal illness

excess or deficiency in the absence of thyroid disease in critically ill patients; Euthyroid Sick syndrome; low TSH, low T3, low T4; changes in thyroid hormone binding protein concentration

227

thyroid nodules

fairly common; require fine needle aspiration for diagnosis