Endocrinology- Embriology, anatomy, Physiology Flashcards
Thyroid development
Thyroid diverticulum arises from floor of primitive pharynx and descends into neck. Connected to tongue by thyroglossal duct. Foramen cecum is normal remnant of thyroglossal duct.
Thyroid follicular cells are derived from endoderm; parafollicular cells (aka, C cells, produce Calcitonin) are derived from neural crest.
Thyroid development
Pathology
Thyroglossal duct cyst presents as an anterior midline neck mass that moves with swallowing or protrusion of the tongue (vs persistent cervical sinus leading to branchial cleft cyst in lateral neck).
Most common ectopic thyroid tissue site is the tongue (lingual thyroid). Removal may result in hypothyroidism if it is the only thyroid tissue.
Adrenal cortex and medulla
- Derived from
Adrenal cortex (derived from mesoderm) and medulla (derived from neural crest).
GFR: Glomerular, fascicular, Reticular
Anterior pituitary (adenohypophysis)
- Derived from
- Hormones it produce
Secretes FSH, LH, ACTH, TSH, prolactin, GH, and β-endorphin. Melanotropin (MSH) secreted from intermediate lobe of pituitary.
*Derived from oral ectoderm (Rathke pouch)
α subunit—hormone subunit common to TSH, LH, FSH, and hCG.
B-FLAT: Basophils—FSH, LH, ACTH, TSH.
Acidophils: GH, PRL.
Posterior pituitary (neurohypophysis
- Derived from
- Hormones it produce
Stores and releases vasopressin and oxytocin, both
made in the hypothalamus (supraoptic and paraventricular nuclei) and transported to posterior pituitary via neurophysins (carrier proteins).
Derived from neuroectoderm.
Endocrine pancreas cell types
α = glucagon (peripheral)
β = insulin (central)
δ = somatostatin (interspersed)
Insulin synthesis
Preproinsulin cleavage of “presignal” proinsulin (stored in secretory granules) cleavage of proinsulin exocytosis of insulin and C-peptide equally.
Insulin and C-peptide are increased in insulinoma and sulfonylurea use, whereas exogenous insulin lacks C-peptide.
Anabolic effects of insulin:
Increase glucose transport in skeletal muscle and
adipose tissue
Increase glycogen synthesis and storage
Increase triglyceride synthesis
Increase Na+ retention (kidneys)
Increase protein synthesis (muscles)
Increase cellular uptake of K+ and amino acids
Decrease glucagon release
Decrease lipolysis in adipose tissue
insulin-independent glucose uptake (organs)
Insulin-dependent glucose transporters
BRICK LIPS: Brain, RBCs, Intestine, Cornea,Kidney, Liver, Islet (β) cells, Placenta, Spermatocytes
GLUT4: adipose tissue, striated muscle
**insulin does not cross placenta.
Insulin Regulation
incretins ([GLP-1], [GIP])
Release decrease by α2, increase by β2 (2 = regulates insulin)
Glucose enters β cells ATP generated from glucose metabolism closes K+ channels and depolarizes β cell membrane . Voltage-gated Ca2+ channels open
Ca2+ influx and stimulation of insulin exocytosis
Glucagon Function and Regulation
Promotes glycogenolysis, gluconeogenesis, lipolysis, and ketone production.
Secreted in response to hypoglycemia. Inhibited by insulin, hyperglycemia, and somatostatin.
Hypothalamic-pituitary hormones
- ADH
- GHRH
water permeability of distal convoluted tubule and collecting duct cells in kidney (AQP2). Stimulus for secretion is Higher plasma osmolality.
Increase GH. Analog (tesamorelin) used to treat HIV‑associated lipodystrophy.
Hypothalamic-pituitary hormones
- CRH
- Dopamine
Increase ACTH, MSH, β-endorphin. Decrease in chornic steroid use.
Decrease prolactin, TSH. antipsychotics (antagonist) can cause galactorrhea.
Hypothalamic-pituitary hormones
- GnRH
- MSH
Increase FSH, LH. Suppressed by hyperprolactinemia.
Tonic GnRH suppresses HPG axis. Pulsatile GnRH leads to puberty, fertility.
Increase melanogenesis by melanocytes. Causes hyperpigmentation in Cushing disease
Hypothalamic-pituitary hormones
- Oxytocin
- Prolactin
Causes uterine contractions during labor. Responsible for milk letdown reflex in response to suckling.
Decrease GnRH Pituitary. prolactinoma cause amenorrhea, osteoporosis, hypogonadism, galactorrhea.
Hypothalamic-pituitary hormones
- Somatostatin
- TRH
Decrease GH, TSH. Analogs used to treat acromegaly.
Increase TSH, prolactin. Increase TRH (eg, in 1°/2° hypothyroidism) may increase prolactin secretion causing galactorrhea.
Prolactin
- Function
- Regulation
Stimulates milk production in breast; inhibits ovulation in and spermatogenesis by inhibiting GnRH.
is tonically inhibited by dopamine from tuberoinfundibular pathway of hypothalamus. Prolactin in turn inhibits its own secretion by increasing dopamine synthesis. TRH increase prolactin secretion.
Dopamine agonists (eg, bromocriptine) can be used in treatment of prolactinoma.
Dopamine antagonists (eg, most antipsychotics) and estrogens (eg, OCPs, pregnancy) stimulate prolactin secretion.
Growth hormone (somatotropin)
- Function
- Regulation
Stimulates linear growth and muscle mass through IGF-1 (somatomedin C) secretion by liver. Increase insulin resistance (diabetogenic).
Secretion increase during exercise, deep sleep, puberty, hypoglycemia. Secretion inhibited by glucose and somatostatin release via negative feedback by somatomedin.
Appetite regulation
- Ghrelin
Stimulates hunger (orexigenic effect) and GH release (via GH secretagogue receptor).
Sleep deprivation or Prader-Willi syndrome increase ghrelin production.
Acts via lateral area of hypothalamus to increase appetite (hunger center).
Appetite regulation
- Leptin
Satiety hormone. Produced by adipose tissue.
Mutation of leptin gene congenital obesity. Sleep deprivation or starvation decrease leptin production.
Acts via ventromedial area of hypothalamus to decrease appetite (satiety center)
Appetite regulation
- Endocannabinoids
Act at cannabinoid receptors in hypothalamus and nucleus accumbens, increase appetite.
*exogenos endocannabinoids cause the munchies
Antidiuretic hormone (vasopressin)
Regulates serum osmolality (V2-receptors) and blood pressure (V1-receptors).
ADH level is decreased in central diabetes insipidus (DI), normal or increased in nephrogenic DI.
Desmopressin (ADH analog) is a treatment forcentral DI and nocturnal enuresis.
Aromatase inhibitors
Anastrozole, exemestane
Adrenal steroids
Pag. 326
Congenital adrenal hyperplasias (17α-hydroxylase)
- Hormones elevated
- Labs
- Presentation
Mineralocorticoids.
Low androstenedione
XY: Genitalia ambiguous, undescended testes.
XX: Lack 2ry sexual development.
Congenital adrenal hyperplasias (21-hydroxylase)
- Hormones elevated
- Labs
- Presentation
Sex hormones
High renin, High 17 hidroxiprogesterone
Presents in infancy (salt wasting) or childhood (precocious puberty)
XX: virilization
*Most common
Congenital adrenal hyperplasias
- Hormone characteristics
- Labs
- Presentation
Decrease aldosterone
Increase 11-deoxycorticosterone (results in increase BP)
Increase sex hormones
Low renin
XX: virilization
Congenital adrenal hyperplasias
All congenital adrenal enzyme deficiencies are characterized by skin hyperpigmentation (due to MSH production) and bilateral adrenal gland enlargement (due to ACTH stimulation).
If deficient enzyme starts with 1, it causes hypertension; if deficient enzyme ends with 1, it causes virilization in females.
Cortisol
- Function
A BIG FIB
Appetite
increase Blood pressure
Insulin resistance (diabetogenic)
Gluconeogenesis, lipolysis, and proteolysis
decrease Fibroblast activity (poor wound healing, collagen synthesis, increase striae)
Decrease Inflammatory and Immune responses
Decrease Bone formation (low osteoblast activity)
- Chronic stress induces prolonged secretion.
- Exogenous corticosteroids can cause reactivation of TB and candidiasis (blocks IL-2 production).
Calcium homeostasis
- Plasma Ca2+ exists in three forms:
Ionized/free (~ 45%, active form)
Bound to albumin (∼ 40%)
Bound to anions (∼ 15%)
Calcium homeostasis
lower pH increase affinity of albumin to bind Ca2+ hypocalcemia (eg, cramps, pain, paresthesias, carpopedal spasm).
Ionized/free Ca2+ is 1° regulator of PTH
Parathyroid hormone
- Function
Chief cells of parathyroid
- Increase bone resorption of Ca2+ and PO4
- Increase kidney reabsorption of Ca2+ in distal convoluted tubule.
- Decrease reabsorption of PO4 3− in proximal convoluted tubule.
- 1,25-(OH)2 D3 (calcitriol) production by stimulating kidney 1α-hydroxylase in proximal convoluted tubule.
Parathyroid hormone
- Regulation
Low serum Ca2+ increase PTH secretion.
High serum PO4 increase PTH secretion.
low serum Mg2+ increase PTH secretion.
Lower serum Mg2+ decrease PTH secretion.
Common causes of low Mg2+ include diarrhea, aminoglycosides, diuretics, alcohol abuse
Calcitonin
- Function
- Regulation
Decrease bone resorption of Ca2+.
Stimulated by High Ca2+.
Calcitonin opposes actions of PTH. Not important in normal Ca2+ homeostasis.
Thyroid hormones (T3/T4) - Function
—6 B’s:
Brain maturation
Bone growth (synergism with GH)
β-adrenergic effects. β1 receptors in heart.
Basal metabolic rate increased (via Na+/K+-ATPase)
Blood sugar (glycogenolysis, gluconeogenesis)
Break down lipids (lipolysis)
Thyroid hormones (T3/T4)
- Source
- Wolff-Chaikoff effect
Follicles of thyroid. 5′-deiodinase converts T4 (the major thyroid product) to T3 in peripheral tissue. Peripheral conversion is inhibited by glucocorticoids, β-blockers and propylthiouracil (PTU).
excess iodine temporarily ⊝ thyroid peroxidase decrease T3/T4 production.
Thyroid hormones (T3/T4) - TGB regulation
Thyroxine-binding globulin (TBG) binds most T3/T4 in blood. Bound T3/T4 = inactive.
Increase TBG in pregnancy, OCP use (estrogen) increase total T3/T4
decrease TBG in hepatic failure, steroids, nephrotic syndrome.
Signaling pathways of endocrine hormones
- AMPc
FLAT ChAMP
FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2-receptor), MSH, PTH, calcitonin, GHRH, glucagon, histamine (H2-receptor)
Signaling pathways of endocrine hormones
- GMPc
BAD
BNP, ANP, EDRF (NO)
Signaling pathways of endocrine hormones
- IP3
GOAT HAG
GnRH, Oxytocin, ADH (V1-receptor), TRH, Histamine (H1-receptor), Angiotensin II, Gastrin
Signaling pathways of endocrine hormones
- Intracellular
PET CAT on TV
Progesterone, Estrogen, Testosterone, Cortisol,
Aldosterone, T3/T4, Vitamin D
Signaling pathways of endocrine hormones
- Receptor tyrosine kinase
Think Growth Factors
Insulin, IGF-1, FGF, PDGF, EGF
Signaling pathways of endocrine hormones
- Nonreceptor tyrosine kinase
PIGGET
Prolactin, Immunomodulators (eg, cytokines IL-2, IL-6, IFN), GH, G-CSF, Erythropoietin, Thrombopoietin
