ENDO 2 Flashcards
The — is a true endocrine gland.
anterior pituitary gland
The posterior pituitary
gland contains
axon
terminals of hypothalamic
neurons
The pituitary gland weighs ~600
mg and is located within the
sella
turcica ventral to the diaphragma
sella.
Anterior Pituitary (6) peptide hormones
• Growth Hormone • Adrenocotricotropin (ACTH) • Thyroid-Stimulating Hormone (TSH) • Follicle-Stimulating Hormone (FSH) • Luteinizing Hormone (LH) • Prolactin
Somatotrophs secrete
GH (30-40% of cells)
Corticotrophs secrete
ACTH (20% of cells)
Thyrotrophs secrete
TSH (3-5% of cells)
Gonadotrophs secrete
LH and FSH (3-5% of cells)
Mammotrophs secrete
Prolactin (3-5% of cells)
Posterior Pituitary (2) peptide hormones
• Antidiuretic Hormone
(ADH)/Vasopressin
• Oxytocin
Adenomas (benign) involving somatotropic cells can cause --- if occurring in children before closure of the long bones’ epiphyseal plates or --- in adults, with musculoskeletal, neurologic, and other medical consequences.
gigantism
acromegaly
Neurons in the hypothalamus synthesize and secrete hypothalamic releasing and inhibiting hormones that control the
endocrine cells in
the anterior pituitary.
The hypothalamic hormones are
released into the
primary
capillary plexus in the median
eminence.
Hypothalamic-Hypophyseal
Portal Blood Vessels carry the
hypothalamic hormones to the
sinuses of the anterior pituitary
gland
The hypothalamic regulatory hormones bind to G-protein coupled receptors in
the various endocrine cells of the
anterior pituitary. Then, through generation of
second messengers (ex. cAMP via Adenylate Cyclase, IP3 and DAG via
Phospholipase C), they either stimulate or inhibit AP hormone secretion.
GH,
a peptide hormone, acts directly on target tissues and as a tropic hormone to the liver, which releases insulin- like growth factor-1 (IGF- 1).
Normal concentration of
GH is the adult is
1.6-3 ng/ml it is higher in children (~6 nmg/ml). Levels can increase to 50 ng/dl during prolonged starvation.
Regulation of Growth Hormone Secretion:
Pulsatile secretion;
lower
concentrations during the day
with highest levels a few hours
after sleep.
Regulation of Growth Hormone Secretion: Stimulated by (5)
starvation (protein deficiency), fasting (hypoglycemia), stress, exercise, and excitement.
Regulation of Growth Hormone Secretion:
High secretion in
neonatal period but decreases in childhood. Peak levels during puberty and then they decline with age.
stimulation of GH release (5)
GHRH dopamine catecholamines excitatory aa thyroid hormone
inhibition of GH release (4)
somatostatin
IGF1
glucose
FFA
Many of the growth and
metabolic effects of GH
are mainly produced by
IGFs (also called
somatomedins).
IGF-1 is produced in most
tissues and acts on
neighboring cells in a
— manner.
paracrine
The — is the major
site of IGF-1 synthesis.
liver
There are – different IGF
binding proteins (ex.
IGFBP-1 and IGFBP-3).
6
Mechanisms
of Action of
GH and IGF-1 (4)
- Growth in nearly all tissues in the body (increased size of cells, mitosis and differentiation of bone and muscle cells) mainly via IGF-1
- Amino acid uptake and protein synthesis in most cells.
- Reduced glucose utilization- decreased uptake, increased hepatic glucose production and increased insulin secretion (insulin resistance; diabetogenic)
- Mobilization of fatty acids from adipose tissue (lipolysis) resulting in increased FFA in blood and use of FFA for energy
Before fusion of the epiphyseal plates,
GH and IGF-1 stimulate
chondrogenesis
and widening of the epiphyseal plates,
followed by bone matrix deposition
stimulating linear growth.
In adults, GH and IGF-1 play a role in
regulating the normal physiology of
bone formation by
increasing bone turnover (increasing bone deposition via the activation of OSTEOBLASTS and also increasing bone resorption via activation of OSTEOCLASTS, though to a lesser extent).
Growth Hormone Excess
- – in Children
- – in Adults
Gigantism
Acromegaly
An MRI shows a pituitary tumor in 90% of
acromegalic patients. These tumors
ordinarily involve the (2); rare ectopic tumors may arise in the
— bone
sella and cavernous sinus
sphenoid
Growth Hormone Excess features (6)
Coarse facial features, large fleshy nose, frontal bossing, jaw malocclusion. Diabetes Mellitus Coronary Heart Disease Kyphosis Hyperhidrosis and oily skin Paresthesias
Treatment for a Pituitary Microadenoma
Surgical resection of the tumor (adenomectomy)
via transphenoidal approach followed by
medication (somatostatin (GHIH) receptor ligand
or GH receptor antagonist).
Oral Manifestations of GH Excess (7)
Thick rubbery skin, enlarged nose, and thick lips
Macrocephaly
Macrognathia
Disproportionate mandibular growth
o Mandibular Prognathism
o Generalized Diastemata
Anterior open bite and malocclusion
(macrognathia and tooth migration)
Macroglossia, Dyspnea, Dysphagia, Dysphonia, Sialorrhea
Hypertrophy of the pharyngeal and laryngeal tissues sleep apnea
Manifestations of Acromegaly/Gigantism; will also show enlarged (2)
frontal sinuses
pituitary fossa
Growth Hormone Deficiency
Causes (5)
- Hypothalamic disorders
- Mutations: GHRH receptor, GH gene, GH receptor, IGF-1 receptor
- Combined pituitary hormone deficiencies (panhypopituitarism)
- Radiation
- Psychosocial deprivation
Growth Hormone Deficiency
Clinical manifestations
Depend on the time of onset and the severity of hormone deficiency.
Complete GH deficiency: (4)
- slow linear growth rates
- normal skeletal proportions
- pudgy, youthful appearance (decreased lipolysis)
- in the setting of cortisol deficiency hypoglycemia
— is the most common form of dwarfism
Achondroplasia
Achondroplasia
autosomal dominant condition
that results from a mutation of FGF-3 receptor in cartilage and brain. This mutation makes
the receptor overly active and it inhibits cartilage growth at growth plates so limb growth is
reduced (growth of the trunk of the body is not impacted).
Oral Manifestations of GH Deficiency (4)
• Disproportionate delayed growth of the skull & facial skeleton leading to small facial appearance.
• Tooth formation & growth of the alveolar regions of the jaws are
abnormal and may be disproportionately smaller than adjacent
anatomic structures
• Solitary Median Maxillary Central Incisor
• Eruption of primary and secondary dentition and shedding of deciduous teeth are delayed.
• Tooth formation & growth of the alveolar regions of the jaws are
abnormal and may be disproportionately smaller than adjacent
anatomic structures (4)
tooth crowding and malocclusion
a high tendency for plaque accumulation
difficulty maintaining good oral hygiene
prone to gingivitis and periodontal disease
Eruption of primary and secondary dentition and shedding of deciduous teeth are delayed.
Management:
correct dental & skeletal malocclusions
The Posterior Pituitary/Neurohypophysis
Contains ~100,000 unmyelinated
axons of neurons whose cells
bodies are in the
hypothalamus
(Paraventricular nucleus and
Supraoptic nucleus).
The Posterior Pituitary/Neurohypophysis secretes (2)
(1) Antidiuretic Hormone (ADH)/Arginine Vasopressin (AVP)
(2) Oxytocin
Both neurohormones are polypeptides of – amino acids.
nine
Both neurohormones are polypeptides of nine amino acids.
While each nucleus synthesize one predominate neurohormone, each can
synthesize and secrete
some of the other neurohormone.
ADH/AVP Mechanism of
Action
Blood Vessels:
– Contraction of vascular
smooth muscle via V1
receptors
ADH/AVP Mechanism of Action
Renal Tubules:
– Binds to V2 receptors in the late distal tubule and collecting duct. – Aquaporin-2 (AQP-2) proteins are then inserted into the apical membrane of tubular epithelial cells, allowing for water reabsorption (along with AQP-3 and AQP-4 on the basolateral membrane).
Stimuli for ADH Secretion (3)
Decreased Blood Volume (Isotonic)
Increased Osmolarity (Isovolemic)
Decreased Blood Pressure
Normally changes in Osmolarity stimulate
— Secretion by the Posterior Pituitary
ADH
Hypodipsia (2)
- Decreased or absent feeling of thirst, which results in reduced intake of water and can cause Hypernatremia.
- A common problem in elderly people, but is also associated with lesions in the hypothalamus (thirst center), head trauma, occult hydrocephalus or subarachnoid hemorrhage.
ADH Imbalances (2)
- Diabetes Insipidus (DI)
* Syndrome of Inappropriate ADH (SIADH)
• Diabetes Insipidus (DI) (2)
– Neurogenic/Central
– Nephrogenic/Peripheral
DI:
Due to either
insufficient production (Neurogenic/Central) or lack of kidney response (Nephrogenic/Peripheral) to ADH.
DI:
Presentation with
Polyuria
Polyuria
Excretion of a large volumes of
urine that is hypotonic and tasteless (insipid)
DI:
Diagnostic test includes a
dehydration test in a controlled
environment.
Other causes of polyuria include:
- Primary ingestion of excess fluid: Primary Polydispia
2. Increased metabolism of ADH (ex. pregnancy)
Syndrome of Inappropriate ADH (SIADH)
Increased and uncontrolled secretion of ADH that causes
volume expansion and hyponatremia.
Syndrome of Inappropriate ADH (SIADH) can result from (3)
surgery, pain, stress,
temperature changes,
tumor, TB, Pneumonia, positive pressure breathing,
Hydrocephalus, Meningitis, HIV, etc.
Mechanisms of Action of Oxytocin (2)
• Stimulates contraction of the uterus towards the end of gestation. • Causes milk ejection from the breasts in lactation.
