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LMP301 (Winter 2022) > L10 - Intro to Endocrine Diseases > Flashcards

L10 - Intro to Endocrine Diseases Flashcards

1
Q

Endocrine system?

A 
Regulates important and diverse physiological functions
• homeostasis
• metabolism
• stress response
• cellular differentiation
• growth and development
• reproduction
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2
Q

Characteristic of endocrine glands?

A
  • ductless glands

* secrete “first” messenger chemicals called hormones

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3
Q

Hormones?

A
  • 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
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4
Q

Hormone action?

A
  • 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
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5
Q

Types of Hormones?

A
  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
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6
Q

Transport of Lipid-soluble Hormones in Blood?

A 
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)
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7
Q

Regulation of hormone release?

A
  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

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8
Q

Hormone Regulation: Neural Control?

A

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

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9
Q

Hormone Regulation: Endogenous rhythmicity?

A

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

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10
Q

Describing Endocrine Disorders?

A

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

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11
Q

Investigation of Endocrine Diseases?

A

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

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12
Q

Endocrine Hyperfunction?

A

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

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13
Q

Hypothalamus: Releasing Hormones?

A
  • Growth hormone-releasing hormone (GHRH)
  • Thyrotrophin-releasing hormone (TRH)
  • Corticotrophin-releasing hormone (CRH)
  • Gonadotrophin-releasing hormone (GnRH)
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14
Q

Hypothalamus: Inhibiting Hormones?

A
  • Somatostatin

* Dopamine (Prolactin-inhibiting factor)

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15
Q

Pituitary Gland: Anterior Pituitary?

A
  • Growth hormone (GH)
  • Thyroid-stimulating hormone (TSH)
  • Adrenocorticotrophic hormone (ACTH)
  • Luteinizing hormone (LH)
  • Follicle-stimulating hormone (FSH)
  • Prolactin (PRL)
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16
Q

Pituitary Gland: Posterior Pituitary?

A
  • Antidiuretic hormone (ADH, Vasopressin)

* Oxytocin

17
Q

Hypothalamic-Pituitary-Target Organ Axis

A

**Check slide 17/30

18
Q

Prolactin: Hormone, Function, Target Organ?

A

Hormone: Polypeptide hormone secreted by lactotrophs in anterior pituitary

Function: Stimulates mammary gland development and milk production

Promotes Lactation

Target organ: Mammary gland

19
Q

Prolactin: Normal regulation?

A
  • 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
20
Q

Hyperprolactinemia: Differential diagnosis?

A
  • nursing, pregnancy
  • stress and medications:
  • Antipsychotic drugs: dopamine antagonists
  • hypothyroidism
  • Prolactinoma
21
Q

Hyperprolactinemia: Clinical presentations?

A

Female:
• amenorrhea, galactorrhea, low libido

Male:
• gynecomastia
• infertility
• Impotence, erectile dysfunction

22
Q

Treatment of macroprolactinomas

A

**Check slide 21/30

23
Q

Growth Hormone: Normal physiology and function?

A

**Check slide 22/30

24
Q

Growth Hormone Excess: Gigantism?

A 
• 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
25
Q

Growth Hormone Excess: Acromegaly?

A

• 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

26
Q

Growth Hormone Excess: Laboratory Investigations?

A

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

27
Q

Growth Hormone Excess: Dynamic tests (provocative tests)?

A

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

28
Q

Growth Hormone Excess: Treatment?

A
  • surgery (same as prolactinoma)
  • medication
  • radiotherapy
  • combinations of surgery, medical and radiotherapy
29
Q

Short Stature (definition and causes)?

A

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

30
Q

Growth hormone insufficiency?

A

• 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

31
Q

Dwarfism?

A

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

32
Q

Dwarfism: Clinical presentations?

A
  • growth retardation in all parts of body
  • immature faces
  • delicate extremities
33
Q

Dwarfism: Growth hormone-related causes?

A 
• 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

LMP301 (Winter 2022) (10 decks)

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