Endocrinology Flashcards
What is the function of endocrine glands?
Endocrine – glands secrete hormone into blood stream which acts at some distant tissue site. Pancreatic insulin (ß-cells) → muscle and fat
What is the function of exocrine glands?
Exocrine – glands secrete non-hormone into ductal system for delivery to distant or adjacent site. Pancreatic enzymes (acinar cells) → intestinal contents
Function of paracrine sys.?
Paracrine – cells secrete hormone that acts directly on other nearby cells Testosterone (Leydig cells) → seminiferous tubules
What are hormones?
Hormones are chemical messengers (signaling molecules) that are secreted directly into the blood, which carries them to organs and tissues of the body to exert their functions. There are many types of hormones that act on different aspects of bodily functions and processes.
What types of substances can be hormones? Where are they secreted/ or derived from?
Proteins or polypeptides: Hypothalamus, pituitary, pancreas, intestines, stomach, kidney, heart, parathyroids, liver.
Steroids: Cholesterol derived
Aromatic amino acid derivatives : Derived from tyrosine
Catchecolamines (soluble, neurological actions)
What are the differences between proteins and steroids concerning solubility and function as hormones?
-Proteins are water soluble and usually circulate without a carrier protein. -They interact with cell membrane receptors. EXAMPLE: -Inducing intracellular protein kinase action (G-coupled proteins) -Steroids are lipid soluble and transported bound to protein. -Internalized into cell, interact with nuclear receptors Modulate gene transcription
What are examples of hormones that are Aromatic amino acid derivatives?
T3 and T4 (Thyroid hormones) -Transported bound to protein -Internalized into cell, interact with nuclear receptors (modulate gene transcription) Catecholamines (epinephrine, norepinephrine, dopamine) —-Soluble —-Mostly neurological actions
What concept does this diagram depict?
The Endocrine “Axis” Concept
Hypothalamic releasing hormones stimulate pituitary secretion of trophic hormones
Trophic hormones stimulate endocrine gland synthesis or secretion of primary hormone
Endocrine hormone binds to specific receptors and effects action at target tissue(s)
Explain the concept of positive & negative feedback.
Negative feedback:
———-An endocrine hormone acts upon either pituitary or hypothalamus to decrease secretion of the releasing factor or trophic hormone responsible for its secretion
———-More common
Positive feedback:
———–An endocrine hormone acts upon either pituitary or hypothalamus to increase secretion of the releasing factor or trophic hormone responsible for its secretion
————Estradiol from developing follicle
Defects in the hypothalamus, pituitary gland and target organs/tissues each represent what level of endocrine disease?
Hypothalamus- Tertiary (rare)
Pituitary- Secondary
Tissues/organs- Primary
Where is the pituitary gland located?
The midline base of the brain
What are the posterior and anterior pituitary?
How does the hypothalamus act upon them?
Anterior pituitary (adeno-hypophysis) – gland nature
————Hypothalamic neurons secrete releasing factors into circulation which directly feeds pituitary
Posterior pituitary (neuro-hypophysis) – neural nature
———–Hypothalamic neurons extend into neurohypophysis and secrete their hormones there
Where are nuerohypophysial hormones made? Examples and their actions?
Synthesized in the hypothalamus and transported via axons for storage in posterior pituitary
Arginine vasopressin (AVP, antidiuretic hormone, ADH)
Cyclic nonapeptide
Acts on kidney tubules to increase water reabsorption
Vasoconstrictor
Hypothalamic osmoreceptors & cardiac/carotid baroreceptors
Oxytocin
Cyclic nonapeptide differs from AVP by two amino acids
Involved in lactation and parturition
Milk letdown
Uterine contraction
Pitocin® – synthetic oxytocin to induce labor
What are the two categories of Adenohypophysial Hormones?
List the hormones in each group.
Direct effector hormones
- Growth hormone (GH, hGH)
- Prolactin (Prl)
Trophic hormones:
- Adrenocorticotropic hormone (ACTH)
- Follicle stimulating hormone (FSH)
- Luteinizing hormone (LH)
- Thyroid stimulating hormone (thyrotropin, TSH)
What secretes Growth Hormone? What inhibits it?
Somatotrophs (secrete GH) comprise over 1/3 of pituitary wt
Stimulated by growth hormone releasing hormone (GHRH) – 44 aa peptide
Inhibited by somatostatin – 14 or 28 aa peptide
——–Hypothalamus and pancreatic δ-cells
HOW is Growth Hormone GH secreted?
Secreted in pulsatile fashion (avg interval 2-3 hrs)
—Greatest secretion during sleep
—Spikes occur after meals and exercise
—Blood GH may be undetectable between pulses
———Poor value of isolated GH blood samples
What are the anabolic actions of GH?
Anabolic:
Increases protein synthesis, esp. in muscle
Soft tissue, bone and cartilage growth
Gluconeogenesis (glucogenic)
What is the catabolic function of GH?
Stimulating lipolyisis.
What does IGF stand for? Examples?
insulin-like growth factor
(IGFs, somatomedins, sulfation factor)
GH stimulates the formation of ______ in the liver acting as a _______hormone as well and the liver an endocrine organ.
IGFs
trophic
What is the most important IGF? Where is it made? What does it respond to? Howis it measured?
IGF-1 – most important IGF
Previously known as somatomedin C
Synthesized by the liver in response to GH
Insulin structural homology
Bound to IGF-binding protein 3 (IGF-BP3)
Both IGF-1 and IGF-BP3 blood levels are positively correlated with GH secretion
Blood levels are more stable than GH
Preferred testing marker (± IGF-BP3)
Measure by immunoassay (limited platforms)
What is the name of this disorder? What is it a result of?
Hypersecretion:
Gigantism – GH excess during growth phase
What is this disorder?
Acromegaly – GH excess after growth complete
commonly result from pituitary tumor
What disorders result from GH HYPOsecretion?
Hyposecretion:
Pituitary dwarfism –
not the same as achondroplasia
Autosomal dominant FGFR3 mutation; homozygous fatal
May result from tumors that interfere with GH secretion
May also result from genetic defects in GHRH gene, GH gene, GH receptor, IGF-1 synthesis or receptor
Adult deficiency
Mental issues (vague) - social withdrawal, fatigue, …
Osteoporosis
Decreased lean body mass (muscle)
Inc. total and LDL cholesterol
How are GH Hypo/Hyper secretion measured?
Immunoassay – random GH sample not necessarily helpful (pulsatile secretion)——-IGF-1 preferred
Hypersecretion:
Oral GTT – should suppress elevated GH to <1 ng/mL
Hyposecretion:
Insulin tolerance test – hypoglycemia (<50 mg/dL)
—–induces GH secretion
——–Requires physician attendance and concurrent glucose testing
Arginine infusion – induces GH (safer that insulin tolerance test)
—-Failure of GH to rise confirms deficiency
How is prolactin unique?
No physiologic releasing hormone
—–TRH (thyrotropin releasing hormone) in pathological situations (e.g., hypothyroidism)
Under tonic (constant) inhibition by dopamine
Only non-peptide releasing hormone
Loss of inhibition leads to uncontrolled secretion
Drugs that affect dopamine affect Prl (anti-psychotics, e.g., phenothiazines, haloperidol, …)
How is prolactin similar to GH? How is it stimulated?
Pulsatile secretion, similar to GH
Stimulated by pregnancy and suckling
What is the purpose/fnxn/action of prolactin?
Primary action is influence on lactation
Requires actions of estrogens, steroids, thyroid
Induces growth of breast ducts and alveoli, milk proteins
Suppresses release of GnRH
Prevents secretion of FSH and LH, thus the downstream effects of those hormones
What is a prolactinoma?
Hypersecretion
Prolactinoma – prolactin secreting pituitary tumor
Prolactin level typically >150-200 ng/mL
Elevation proportional to tumor size
Be aware of potential hook effect
More obvious in females
Amenorrhea (GnRH suppression) and galactorrhea (breast milk)
Pituitary stalk damage – dec. dopamine delivery
Hypothyroidism (1° or 2°) – increased TRH
Venipuncture, breast exam (25-50 ng/mL)
Anti-dopaminergic drugs (esp. anti-psychotics)
How is prolactin measured?
Immunoassay (sandwich typically)
Reference intervals are method dependent
Males 5-21 ng/mL, females 6-30 ng/mL
———–Increased in pregnancy
Why would you need a dilution protocol for measuring prolactin?
Hook effect
What is macroprolactin?
Macroprolactin – IgG bound prolactin (physiologically inactive)
Increased level due to reduced renal clearance
Precipitate with 12.5% PEG 6000 (1+1 with 25%)
14% of native prolactin may precipitate
Most common cause of (milder) hyperprolactinemia?
What is pan hypopituitarism?
What causes it?
Nothing is being secreted
Pituitary tumors
Parapituitary or hypothalamic tumors
Trauma, e.g., pituitary stalk section
Radiation therapy or cranial surgery
Infarction (postpartum: Sheehan’s syndrome)
Infection
Loss of direct effector hormones less apparent
Recombinant GH Rx in children, adults less common
Loss of tropic hormones more critical and obvious
Replace missing primary hormones as needed
Describe Thyroid location and physiology.
Thyroid gland (18-60 g) straddles trachea (left and right lobes, connected by isthmus)
Four parathyroids on back of gland, 2 each lobe
How are Throid cells arranged?
Thyroid cells arranged as follicles: Colloid and parafollicular
What is Colloid primarily made of?
Colloid primarily thyroglobulin (Tg):
Tg - tyrosine rich protein ~660 kD
Thyroid actively takes up iodine
Iodination of Tg tyrosine residues
Coupling of Tg tyrosine side chains
Release of thyroxine (T4)
-and triiodothyronine (T3)
What does the thyroid parafollicular cells secrete? Is it significant in the clinical lab?
- Calcitonin
- No
What is TPO?
What is it’s significance?
Thyroid peroxidase
What is TRH?
Thyrotropin releasing hormone (TRH)- Stimulates release of thyrotropin
3 amino acid peptide (can also stimulate release of prolactin)
What is TSH?
Thyrotropin (thyroid stimulating hormone, TSH)
28 kD peptide, α- and ß-subunits (identifiable via beta)
α-subunit identical with α-subunit of FSH, LH and hCG
Stimulates thyroid cell proliferation
Stimulates thyroid hormone production/secretion
What is T4 and T3?
Thyroxine (T4) and Triiodothyronine (T3)
Physiologically active hormones (esp. T3)