Intro to Endocrinology Flashcards
Spring 2024
Hormone
Chemical substance that sends a message to another cell in the body
Give example of endocrine, exocrine, neurocrine, and paracrine cellular messaging
Endocrine: bloodstream
Exocrine: GI tract
Neurocrine: neurologically
Paracrine: interstitial fluid
List the glands that we cover
- Hypothalamus
- Pituitary
- Thyroid
- Parathyroid
- Adrenal gland
- Pancreas
- Ovaries
- Testes
List the 6 hormone classifications
- Amine
- Peptide
- Protein
- Glycoprotein
- Steroid
- Fatty acid
Amine hormones
- Trp or Tyr are modified to create amine hormones
- Epinephrine, triiodothyronine, thyroxine, serotonin
- Very short half-lives
Peptide hormones
- Chain < 50 aa
- Water soluble, don’t cross membranes easily
- Must first bind to membrane-bound receptors
- Vasopressin and oxytocin
Protein hormones
- Chain > 50 aa
- ACTH, calcitonin, insulin, glucagon, oxytocin
Glycoprotein hormones
- Conjugated to carbs
- FSH, LH, and TSH
- Solubility and half-life similar to protein hormones
Steroid hormones
- Derived from lipid, usually cholesterol
- Hydrophobic, must be transported in blood bound to carrier proteins
- Can cross membranes due to lipids
- Aldosterone, cortisol, estrogen, progesterone, testosterone, other androgens (DHEA)
Fatty acid hormones
- Derivatives of arachidonic acid
- Eicosanoids, leukotrienes, prostaglandins, thromboxanes
- Rapidly degraded, effective for only seconds
Metabolism
The sum of chemical processes that occur within a living organism to maintain life (catabolism + anabolism)
Anabolism
Creating substances
Catabolism
Breaking down substances
Hormone metabolism
The speed of anabolism or catabolism determines the extent to which hormones are capable of binding to receptors and eliciting effects
Conditions that modify hormone metabolism/levels
- Speed of production or breakdown affects blood hormone levels
- Amount of carrier protein affects protein-bound hormone levels
- Disease states (e.g., cirrhosis) affect enzymatic hormone breakdown
Effects of alcohol consumption on hormone metabolism
- Increase testosterone degradation
- Leads to cirrhosis, which can cause less albumin and other binding proteins
Adrenal steroid hormone synthesis
Many hormones are produced in the adrenal gland by a cascade of enzymatic reactions
Which two organs predominantly eliminate hormones?
Kidney and liver
General mechanism for hormone elimination
Blood -> Liver tags certain hormones for destruction or creation of different substances (or kidney)
Steroid hormone elimination mechanism
Inactivating metabolic pathways and excretion in urine or bile
Thyroid hormone excretion mechanism
Inactivated by intracellular deiodinases
Catecholamine hormone excretion mechanism
Rapidly degraded within blood circulation
Fatty acid derivative hormone excretion mechanism
Rapidly inactivated by metabolism and typically active for a short time period (seconds)
Negative feedback
A stimulus will feedback upstream and decrease production of itself (e.g., thyroid)
Positive feedback
Increase the stimulus received until a distinct endpoint is achieved (e.g., coagulation cascade)
Thyroid negative feedback mechanism
:)
Primary endocrine disorder
Thyroid main problem because lack thyroid hormones (T3, T4)
Secondary endocrine disorder
Pituitary is the problem. Lack TSH
Tertiary endocrine disorder
Hypothalamus is the problem. Lack TRH
List factors that affect hormone levels
I would review slide details for these
- emotional stress
- time of day
- menstrual cycle
- menopause
- diet
- drugs
List the 3 distinct parts of the pituitary
- anterior pituitary
- intermediate lobe
- posterior pituitary
Posterior pituitary
- Arises from diencephalon
- Responsible for storage/release of oxytocin and AVP/ADH
Anterior pituitary
Receives 80%-90% of blood supply and many hypothalamic factors via the hypothalamic-hypophyseal portal system
When can pituitary function be gestationally detected?
Between 7th and 9th week
Lactotrophs
Prolactin-secreting cells
Somatotrophs
GH-secreting cells
Thyrotrophs
TSH-secreting cells
Corticotrophs
ACTH-secreting cells
Gonadotrophs
LH- and FSH-secreting cells
Afferent pathways (inputs) to the hypothalamus
Integrated in various specialized nuclei and then resolved into specific responses
Relate the hypothalamus’ many efferent (output) neural connections to higher brain centers to responses for each specific pituitary hormone
The responses are similar for each hormone and characterized by negative feedback mechanisms, pulsatility, and diurnal variation
Give example of endocrine feedback loop
Hypothalamic-pituitary-thyroidal axis
Thyroid secretes thyroxine to act on hypothalamus
How are all anterior pituitary hormones secreted? Examples?
Pulsatile fashion, such as LH and FSH
How is pulse frequency of secretion regulated?
Neural modulation and is specific for each hypothalamus-pituitary-end organ unit
Which hormone’s secretion profile does GnRH pulse frequency affect?
LH
Hormones with diurnal variation
- ACTH (trough 11pm-3am, peak 6am-9am
- TSH nocturnal levels 2x daytime levels
T/F
According to autopsy studies, up to 50% of people harbor clinically silent pituitary adenomas
False, 20%
T/F
Pituitary tumors are found in 10-30% of normal individuals undergoing MRI exams
True
T/F
Pituitary tumors account for 78% of lesions from patients who have undergone transsphenoidal surgery
False, 91%
When can pituitary enlargement be seen?
Puberty and pregnancy
List tumors in order of clinical significance
- Prolactin-secreting
- “null cell”
- TSH, GH, ACTH, or gonadotropin-secreting
List anterior pituitary hormones plus functions
- GH = tissue growth
- TSH = thyroid hormones
- ACTH = cortical hormones
- FSH = testes/ovaries
- LH = testes/ovaries
- PRL (prolactin) = breast glandular tissue
List posterior pituitary hormones
- oxytocin = uterine contraction/lactation
- ADH/AVP/vasopressin = kidney water reabsorption
Compare hormones secreted from anterior pituitary (AP) to those secreted from hypothalamus
- AP hormones are larger and more complex
- May be tropic or direct effectors
Tropic hormones
Actions are specific for another endocrine gland
Direct effectors
Directly act on peripheral tissue
Hypothalamic-pituitary target organ axis
:)
Role of pituitary gland and why
Vital for normal growth because it secretes somatotropin aka growth hormone
Effect or removing the pituitary
Growth ceases
Also ceases if hormonal products from other endocrine glands acted on by anterior pituitary are replaced
How do you restore growth?
Administer GH
Somatotropin
Same as growth hormone, which is pulsatile
Why is GH amphibolic?
Bc it directly influences both anabolic and catabolic processes
How does GH affect fasting/fast states?
- Allows person to transition from fed to fasting state
- No shortage of normal intracellular oxidation substrates
How does GH affect insulin/glucose metabolism?
- Inhibits insulin effects
- Promotes hepatic gluconeogenesis and lipolysis
- Lipolysis enhanced by providing oxidative substrates for peripheral tissue and conserves glucose for CNS by stimulating hepatic delivery of glucose/inhibiting insulin-mediated glucose metabolism
Is GH a tropic hormone or direct effector?
Direct effector on many peripheral tissues
Insulin-like growth factor (IGF)
- Growth factor induced by GH in liver
- Cell surface receptors distinct from insulin, but IGF-2 can cross-react with insulin receptor and cause hypoglycemia
- Mediates indirect effects of GH
T/F
Single random GH measurement is diagnostic
False, it’s rarely diagnostic
GH measurement has limited value
GH testing
- Baseline measurements helpful
- Interpret in conjunction with glucose suppression tests to diagnose acromegaly
- Interpret in conjunction with GH stimulation test to diagnose GH deficiency
How to diagnose acromegaly in childhood/adolescence
- Glucose tolerance test and measuring IGF-1 (preferred)
- IGF-1 useful in eval excess/deficient growth disorders in both adults and children
- IGF-1 can monitor recombinant GH treatment and follow-up
Strategies to stimulate GH
- Insulin-induced hypoglycemia (outdated)
- Combo infusions of GHRH and L-arginine
- Infusion of L-arginine coupled with oral L-DOPA
Acromegaly
- Pathologic or autonomous GH excess, usually result of tumor
- If GH-producing tumor occurs before epiphyseal closure of long bones, then gigantism results
What happens if GH-producing tumor happens after puberty?
- Classical/insidious features: bony and soft tissue overgrowth
- Progressive enlargement of hands and feet, growth of facial bones (mandible/skull), teeth gaps, arthritis, sleep apnea, excess sweating/heat intolerance
Acromegaly treatment
- Tumor ablation with continued function of remaining pituitary
- Transsphenoidal adenctomy procedure of choice
- External beam/focused irrradiation may take several years to take full effect
- Treatment does NOT reverse bone growth effects
How does GH deficiency manifest in children
Growth failure
Not all short pts have GH deficiency
How does GH deficiency manifest in adults?
- Complete or partial anterior pituitary failure
- Vague symptoms: social withdrawal, fatigue, loss of motivation, diminished feeling of well-being
- Osteoporosis and body composition alterations
Prolactin
- Structurally related to GH and human placental lactogen
- Stress hormone
- Vital functions in reproduction
- Unique due to tonic inhibition as mode of hypothalamic regulation instead of intermittent stimulation
Prolactinoma
- Pituitary tumor that secretes prolactin, most common functional pituitary tumor
- Clinical presentation depends on pt age/gender, tumor size
Prolactin-inhibitor factor
Dopamine
Only neuroendocrine signal that inhibits prolactin
Management of prolactinoma
- Reducing tumor mass
- Restoring normal gonadal function/fertility
- Preventing osteoporosis
- Preserving normal anterior/posterior pituitary function
- Therapeutic options: simple observation, surgery, radiotherapy, medical management with dopamine agonists
Prolactin > 150ng/mL indicates what cause?
- Prolactinoma
- Degree of elevation correlates with tumor size
Prolactin 25-100 ng/mL indicates what causes?
- Pituitary stalk interruption
- Dopaminergic antagonist meds
- Primary thryoidal failure
- Renal failure
- Polycystic ovary syndrome
Clinical eval of hyperprolactinemia
- History/physical exam usually enough to exclude most common non-endocrine causes
- Essential to obtain TSH and free T4 to eliminate primary hypothyroidism as a cause for the elevated prolactin
- If pituitary tumor sus, assess other anterior pituitary function: ACTH/cortisol, LH, FSH, gender-specific gonadal steroids, MRI
Idiopathic galactorrhea
- Lactation in women with normal prolactin levels
- Usually seen in women who have gotten pregnant several times and no pathological implication
Hyperprolactinemia associated with…?
- Renal failure
- Cirrhosis
- Hypothyroidism
- Trauma
- Inflammation
- Drugs (TCS, phenothiazine’s, reserpine)
- Adrenal insufficiency
- Prolactinoma
Clinical manifestation of prolactinoma in non-postpartum women and women with amenorrhea
- Galactorrhea 30-%0&
- Menstrual irregularity
- Infertility
Clinical manifestation of prolactinoma in men
- Hypogonadism
- Erectile dysfunction
- Galactorrhea < 30%
- Visual abnormalities
- Extra-ocular muscle weakness
- Headache
Panhypopituitarism
Complete loss of anterior pituitary function due to failure of either pituitary or hypothalamus
Monotropic hormone deficiency
Loss of single pituitary hormone
Lab diagnosis of hypopituitarism
- Straight-forward
- Primary failure of endocrine gland accompanied by dramatic increases in circulating levels of corresponding pituitary tropic hormone
- Secondary failure (hypopituitarism) associated with low or normal levels of tropic hormone
Etiology of hypopituitarism
- Various types of tumors
- Postpartum ischemic necrosis of pituitary
- Infiltrative diseases such as hemochromatosis, sarcoidosis, histiocytosis
- Fungal infections, TB, syphilis
- Lymphocytic hypophysitis
- Severe head trauma, pituitary surgery, radiotherapy
Panhypopituitarism treatment
- Thyroxine, glucocorticoids, gender-specific sex steroids
- Replacement therapy tricker in patients who desire fertility
Posterior pituitary
Extension of forebrain and represents the storage region for AVP and oxytocin
Where are AVP and oxytocin synthesized?
- Supraoptic and paraventricular nuclei of the hypothalamus and transported to the neurohypophysis via axons in the hypothalamoneurohypophyseal tract
- Also made outside of hypothalamus in various tissues
Synthesis of AVP and oxytocin tightly linked to production of ______
Neurophysin
Oxytocin
- Critical role in lactation, labor, and parturition (childbirth)
- Secretion responds to positive feedback loop
- Uterine contractions propagate oxytocin release, causing more contractions
- Maternal nurturing and mother-infant bonding
- Effects on pituitary, renal, cardiac, metabolic, and immune function
Pitocin
Synthetic oxytocin
AVP major action
Regulate renal free water excretion
Where are vasopressin receptors in kidney concentrated?
Renal collecting tubules and ascending limb of loop of Henle
Other AVP functions
- Potent pressor agent (elevates BP)
- Affects blood clotting by promoting Factor VII release from hepatocytes
- Von willebrand factor release from endothelium
How dos plasma osmolality increase affect AVP secretion?
Increases vasopressin secretion
Osmoreceptors very sensitive to even small changes
What happens to AVP release if blood pressure or volume fall?
Vascular baroreceptors initiate AVP release
How is AVP regulated?
By hypothalamic osmoreceptors and vascular baroreceptors
Diabetes insipidus
AVP deficiency or resistance
AVP excess
- Much more difficult to treat than deficiency due to free water retention
- Restricting free water intake to small amounts each day has been main treatment
