L10 - Intro to Endocrine Diseases

Question 1

Endocrine system?

Answer 1

Regulates important and diverse physiological functions
• homeostasis
• metabolism
• stress response
• cellular differentiation
• growth and development
• reproduction

Question 2

Characteristic of endocrine glands?

Answer 2

• ductless glands

* secrete “first” messenger chemicals called hormones

Question 3

Hormones?

Answer 3

• are carried to distant target cells via the bloodstream
• act on target cells that possess receptors sensitive to the hormone
• relatively slow compared to nervous system
• Examples: thyroid hormone, insulin, testosterone, growth hormone, aldosterone, cortisol

Question 4

Hormone action?

Answer 4

• Autocrine: hormones that have a local effect on itself
• Paracrine: hormones that have a biological effect on nearby cells
• Endocrine: hormones secreted into blood vessel that have biological effect downstream

Question 5

Types of Hormones?

Answer 5

1. Peptide/protein hormones: Water soluble
   • Released into blood and requires no carrier protein for distribution
   • Generally very short half-life (~seconds to minutes)
   • Bind to cell surface receptors and signals through 2nd messenger systems –signal transduction
   • Processed from larger precursors -prohormone and preprohormone
2. Lipid Soluble Hormones
   • steroid hormones: cholesterol-based structure
   • e.g. cortisol, aldosterone, testosterone, estradiol
   • thyroid hormones: tyrosine-ring structure
   • highly protein-bound in blood
   • free hormone diffuses directly into cells to bind to cytosolic or nuclear receptors

Question 6

Transport of Lipid-soluble Hormones in Blood?

Answer 6

Lipid-soluble hormones require carrier proteins in order to circulate within the bloodstream
• have a long half life (~hours)
• bound fraction permits prolonged and steady hormone action
• binding can be:
- specific 
\+ thyroxine binding globulin (TBG)
\+ cortisol binding globulin (CBG)
\+ sex hormone binding globulin (SHBG)
- non-specific
\+ albumin
\+ transthyretin (prealbumin)

Question 7

Regulation of hormone release?

Answer 7

1. Humoral and hormonal stimuli
   • Humoral: extracellular fluid composition e.g. high glucose triggers insulin release
   • Hormonal: response to other hormones e.g TSH triggers T4 and T3 production
   -> Hypothalamic-pituitary-primary gland axis
2. Feedback loops
   • Positive feedback
   - increase in hormone stimulates further secretion e.g. estrogen in menstrual cycle
   • Negative feedback
   - increase in hormone inhibits further secretion
   - “thermostat”
   - necessary for maintaining levels in a controlled range and limiting extremes in hormone secretion
   - most common feedback

-> basis of endocrine lab testing and interpretation

Question 8

Hormone Regulation: Neural Control?

Answer 8

evokes or supresses hormone secretion in response to
• External stimuli: visual, auditory, olfactory
• Internal stimuli: pain, emotion, fright

Question 9

Hormone Regulation: Endogenous rhythmicity?

Answer 9

• Diurnal rhythm: day-night
- Growth hormone, prolactin
• Circadian (around a day) rhythm
• Pulsatile

Question 10

Describing Endocrine Disorders?

Answer 10

Functional state prefixes:
• Hyper-: hormone above normal level (over secretion)
• Hypo-: hormone below normal level (undersecretion)
• Eu-: hormone within normal range
• e.ghypoaldosteronism, hyperinsulinism, euthyroid

Level of the abnormality:
• Primary: abnormality in the peripheral gland
• Secondary: abnormality in stimulation from pituitary
• Tertiary: abnormality in stimulation from hypothalamus

Question 11

Investigation of Endocrine Diseases?

Answer 11

Laboratory investigation
• Blood total hormone measurement
• Blood free hormone measurement
• Calculated hormone values and indices

Dynamic tests (provocative tests)
• Tests to assess the dynamic responses of hormonal and metabolic axes
1. Stimulation of a hormonal axis by releasing hormones or other exogenous agents
2. Attempted suppression of a hormonal system
3. Physiological stimulation or challenge of a metabolic or hormonal system
• blood collection at baseline and post stimulation/suppression time-points

Question 12

Endocrine Hyperfunction?

Answer 12

Overstimulation
• gland overstimulation and hyperplasia
• exogenous stimulation
• gland inflammation/damage (transient)

Adenoma
• slow-growing benign tumor that starts in epithelial tissue of gland
• arises along endocrine gland
• functioning versus non-functioning types
- functioning cause overproduction of hormones
- non-functioning don’t produce hormones; cause disease by mass effect

Ectopic secretion
• inappropriate production and release of hormone by cancerous cells in tissues that do not normally produce the hormone

Question 13

Hypothalamus: Releasing Hormones?

Answer 13

• Growth hormone-releasing hormone (GHRH)
• Thyrotrophin-releasing hormone (TRH)
• Corticotrophin-releasing hormone (CRH)
• Gonadotrophin-releasing hormone (GnRH)

Question 14

Hypothalamus: Inhibiting Hormones?

Answer 14

• Somatostatin

* Dopamine (Prolactin-inhibiting factor)

Question 15

Pituitary Gland: Anterior Pituitary?

Answer 15

• Growth hormone (GH)
• Thyroid-stimulating hormone (TSH)
• Adrenocorticotrophic hormone (ACTH)
• Luteinizing hormone (LH)
• Follicle-stimulating hormone (FSH)
• Prolactin (PRL)

Question 16

Pituitary Gland: Posterior Pituitary?

Answer 16

• Antidiuretic hormone (ADH, Vasopressin)

* Oxytocin

Question 17

Hypothalamic-Pituitary-Target Organ Axis

Answer 17

**Check slide 17/30

Question 18

Prolactin: Hormone, Function, Target Organ?

Answer 18

Hormone: Polypeptide hormone secreted by lactotrophs in anterior pituitary

Function: Stimulates mammary gland development and milk production

Promotes Lactation

Target organ: Mammary gland

Question 19

Prolactin: Normal regulation?

Answer 19

• Prolactin synthesis and secretion tonically inhibited throughout life by dopamine from the hypothalamus
• TRH is weakly stimulatory, but dopamine dominates
• In late pregnancy, high estrogens stimulate prolactin directly and nursing disinhibits dopamine action
• Medications e.g. dopamine antagonist antipsychotics lead to disinhibition

Question 20

Hyperprolactinemia: Differential diagnosis?

Answer 20

• nursing, pregnancy
• stress and medications:
• Antipsychotic drugs: dopamine antagonists
• hypothyroidism
• Prolactinoma

Question 21

Hyperprolactinemia: Clinical presentations?

Answer 21

Female:
• amenorrhea, galactorrhea, low libido

Male:
• gynecomastia
• infertility
• Impotence, erectile dysfunction

Question 22

Treatment of macroprolactinomas

Answer 22

**Check slide 21/30

Question 23

Growth Hormone: Normal physiology and function?

Answer 23

**Check slide 22/30

Question 24

Growth Hormone Excess: Gigantism?

Answer 24

• pituitary gigantism caused by excess secretion of GH prior to closure of epiphyseal growth plates in long bone
• nearly always caused by pituitary adenoma
• Clinical features:
- abnormal height
- large hands and feet
- coarse facial features
- loss of libido
- hyperglycemia

Question 25

Growth Hormone Excess: Acromegaly?

Answer 25

• Increased GH secretion after fusion of bony epiphyses causes acromegaly • acromegaly: hypersecretion of GH which is caused by the existence of a secreting tumor • Clinical features - coarse facial features - soft tissue thickening e.g. lips - protruding jaw - characteristic ‘spade-like’ hands - excessive sweating - impaired glucose tolerance or secondary diabetes

Question 26

Growth Hormone Excess: Laboratory Investigations?

Answer 26

• serum growth hormone (GH) • best screening test for acromegaly is IGF-1 - useful marker in evaluation and monitoring treatment

Question 27

Growth Hormone Excess: Dynamic tests (provocative tests)?

Answer 27

Oral glucose tolerance test (GTT) for acromegaly • collect blood sample: baseline GH • give glucose drink • blood sample collection at 60 and 120 minutes

Question 28

Growth Hormone Excess: Treatment?

Answer 28

* surgery (same as prolactinoma) * medication * radiotherapy * combinations of surgery, medical and radiotherapy

Question 29

Short Stature (definition and causes)?

Answer 29

Definition of short stature: • height below 3rd percentile or less than 2SD below the median height for that age & sex according to the population standard Causes: • neurological • gastrointestinal/malabsorption syndromes • nutritional: deprivation of protein and/or calories • cytogenetics: chromosomal abnormalities • endocrinopathies

Question 30

Growth hormone insufficiency?

Answer 30

• deficient growth hormone produced by pituitary • congenital or can develop later in life or acquired (brain trauma, cancer treatment) and genetic defects • no clear cause sometimes • laboratory test: IGF-1 levels • normal reference ranges are gender-and age-specific (and assay specific) and need to be interpreted carefully • Dynamic testing: - growth hormone stimulation test - e.g. clonidine, arginine (i.v.), insulin - GH secretion by stimulating GHRH

Question 31

Dwarfism?

Answer 31

condition of short stature, generally defined as an adult height of 4 feet 10 inches (147 cm) or less

Question 32

Dwarfism: Clinical presentations?

Answer 32

* growth retardation in all parts of body * immature faces * delicate extremities

Question 33

Dwarfism: Growth hormone-related causes?

Answer 33

``` • Pituitary Dwarfism: - congenital failure of GH production - low IGF-1, low GH • Laron Dwarfism - congenital absence of peripheral GH receptor - low IGF-1, high GH ```