L10 - Intro to Endocrine Diseases Flashcards
Endocrine system?
Regulates important and diverse physiological functions • homeostasis • metabolism • stress response • cellular differentiation • growth and development • reproduction
Characteristic of endocrine glands?
- ductless glands
* secrete “first” messenger chemicals called hormones
Hormones?
- 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
Hormone action?
- 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
Types of Hormones?
- 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 - 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
Transport of Lipid-soluble Hormones in Blood?
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)
Regulation of hormone release?
- 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 - 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
Hormone Regulation: Neural Control?
evokes or supresses hormone secretion in response to
• External stimuli: visual, auditory, olfactory
• Internal stimuli: pain, emotion, fright
Hormone Regulation: Endogenous rhythmicity?
• Diurnal rhythm: day-night
- Growth hormone, prolactin
• Circadian (around a day) rhythm
• Pulsatile
Describing Endocrine Disorders?
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
Investigation of Endocrine Diseases?
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
Endocrine Hyperfunction?
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
Hypothalamus: Releasing Hormones?
- Growth hormone-releasing hormone (GHRH)
- Thyrotrophin-releasing hormone (TRH)
- Corticotrophin-releasing hormone (CRH)
- Gonadotrophin-releasing hormone (GnRH)
Hypothalamus: Inhibiting Hormones?
- Somatostatin
* Dopamine (Prolactin-inhibiting factor)
Pituitary Gland: Anterior Pituitary?
- Growth hormone (GH)
- Thyroid-stimulating hormone (TSH)
- Adrenocorticotrophic hormone (ACTH)
- Luteinizing hormone (LH)
- Follicle-stimulating hormone (FSH)
- Prolactin (PRL)
Pituitary Gland: Posterior Pituitary?
- Antidiuretic hormone (ADH, Vasopressin)
* Oxytocin
Hypothalamic-Pituitary-Target Organ Axis
**Check slide 17/30
Prolactin: Hormone, Function, Target Organ?
Hormone: Polypeptide hormone secreted by lactotrophs in anterior pituitary
Function: Stimulates mammary gland development and milk production
Promotes Lactation
Target organ: Mammary gland
Prolactin: Normal regulation?
- 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
Hyperprolactinemia: Differential diagnosis?
- nursing, pregnancy
- stress and medications:
- Antipsychotic drugs: dopamine antagonists
- hypothyroidism
- Prolactinoma
Hyperprolactinemia: Clinical presentations?
Female:
• amenorrhea, galactorrhea, low libido
Male:
• gynecomastia
• infertility
• Impotence, erectile dysfunction
Treatment of macroprolactinomas
**Check slide 21/30
Growth Hormone: Normal physiology and function?
**Check slide 22/30
Growth Hormone Excess: Gigantism?
• 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
Growth Hormone Excess: Acromegaly?
• 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
Growth Hormone Excess: Laboratory Investigations?
• serum growth hormone (GH)
• best screening test for acromegaly is IGF-1
- useful marker in evaluation and monitoring treatment
Growth Hormone Excess: Dynamic tests (provocative tests)?
Oral glucose tolerance test (GTT) for acromegaly
• collect blood sample: baseline GH
• give glucose drink
• blood sample collection at 60 and 120 minutes
Growth Hormone Excess: Treatment?
- surgery (same as prolactinoma)
- medication
- radiotherapy
- combinations of surgery, medical and radiotherapy
Short Stature (definition and causes)?
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
Growth hormone insufficiency?
• 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
Dwarfism?
condition of short stature, generally defined as an adult height of 4 feet 10 inches (147 cm) or less
Dwarfism: Clinical presentations?
- growth retardation in all parts of body
- immature faces
- delicate extremities
Dwarfism: Growth hormone-related causes?
• 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
