Endocrine Flashcards
Why is Endocrine System Important
- Growth and development
- Response to stress and injury
- Reproduction
- Regulation of energy metabolism
- Ionic hemostasis
What is the Biologically Critical Ions
Sodium (NA): 135 -145 mEq/L
Potassium (K): 3.5 - 5.0 mEq/L
Cacium (Ca): 8.5 - 10.5 mg/dL
Magnesium (Mg): 1.5 - 2.5 mg/dL
- CO2 & HCO3 is also important
Why is Ionic Homestasis important?
A Proper ionic balance essential for muscle coordination, heart function, nerve function, fluid absorption and excretion (Blood Volume, Blood Pressure).
- Serum Osmolarity: 280-290 mOsmol/kg
- Serum pH: 7.35-7.45
- Outside this range cell, organs dysfunction and death occur
Ions conduct electricity and are found in body fluid, tissue, and blood
- Cell membrane potential
- CNS, CV, Epithelial cell polarization
Is every endocrine dysfunction caused by endocrine disorder
No it is not only caused by it.
- There can be other reasons too like diabeites
Endocrine Disease
Indolent Progression (grow slowly and doesn’t cause pain)
Hormone-secreting cells widely distributed in the body in all organs
- Non specific presentation
– Subclinical syndromes
Differential diagnosis is critical
Endocine Organs
Majority of them are EPITHELIAL
- Secretion hormones => Vascular organs (Ductless)
– It got a regulated release of products
- Ability to modulate activity: structure
- Variable storage reserve
Disease/Dysfunctions
- Under-activity / Over-activity
- Neoplasia
- Autoimmune disease (esp. vulnerable to it)
Endocrine Tissue Classification
- Neuroendocrine system
- Steroid hormone-secreting cells
- Epithelium Thyroid
Neuroendocrine system
Origin:
- Epithelial (pituitary, Islet, endocrine cells, lung, gut)
- Endodermal
- Neuroecttoderm (adrenal medulla, paraganglia, thyroid parafollicular C cells, parathyroid gland)
Produce:
- Peptide hormones (many can function as neurotransmitters)
Characterized by
- Well-developed RER for peptide synthesis
- Large Glgi complexes for packaging
- Numerous SECRETORY GRANULES
– they store and transport hormones to the cell surface for release by exocytosis
Steroid Hormone-Secreting Cells
Arise from the mesodrem (adrenal cortex and steroidogenix cells of the testes and ovaries)
Produce:
- They take cholesterol and produce fat soluble hormones (glucocorticoids, mineralocorticoids, estrogens, testosterone and its precursors.)
Characterized by
- Well developed SER
- Large mitochondria (can metabolize cholesterol throught expression of side chain cleavage)
Thyroid Follicular Epithelium
‘unique’ epithelial cell type of endodermal origin
Synthesize and produce THYROID HORMONES
Characterized by
- Tight junction (needed for critical follicular structures that are the site of storage)
- Prominent microvilli (necessary for reabsorption of that substance for thyroid hormone synthesis)
What is a Hormone?
A chemical substance that can affect the tissues of the body
Water-Soluble Hormones (can’t get into the cell)
- bind to receptor (GPCRs) at the cell surface
- Triggers the activation and/or production of intracellular proteins/enzymes
Lipid-Soluble Hormones
- Hormone-receptor complex binds to a
specific site on the promoter region on DNA
- Activates RNA polymerase
- Stimulates DNA transcription
- Production of intracellular proteins/enzymes
Cellular Mechanisms of Hormone Actions
Target Cells:
- Express hormone receptor which bind to hormones
- Hormone-receptor binding initiates a signal to modulate cellular function
Sensitivity of a target cell to a homone can be Upregulated or Downregulated
- Receptor mutation (insensitivity)
- Hormone mutation (Gain of function, Loss of function, polymorphisms)
Hierarchical Control of Hormone Release
Hypothalamus (Release Hormones) ==> Anterior Pituitary (Stimulating Hormones) ==> Adrenal ==> Cell and tissues of the body
Posterior pituitary hormones
Antidiuretic Hormones (ADH)
Oxytocin
Anterior Pituitary Hormones
- Growth hormone (GH)
- Adrenocorticotropin (ACTH)
- Thyroid-stimulating hormone (TSH)
- Follicle stimulating hormone (FSH)
- Luteinizing hormone (LH)
Antidiuretic Hormone
Water-soluble
Maintain blood pressure, blood volume and tissue water content by controlling the amount of water urinated
Major Stimuli
- Hyperosmolarity (↑POSM); sensed in hypothalamic nuclei
- Volume depletion; sensed by carotid baroreceptors
ADH co-produced and released with CRH (Corticotropin-releasing hormone)
ADH MOA
1) ADH attaches to V2 receptor
2) Activate cascade through Gs protein, adenylyl cyclase, cAMP, and PKA (protein kinase A)
3) Caused insertion of aquaporin 2 into apical membr
4) H2O moves through aquaporin 2 in response to osmotic gradient and go into the basolateral membrane
This result in increasing Blood Volume and decreasing Urine Volume
Receptors are located in the Collecting ducts of the kidney
Dysfunction of the Posterior Pituitary
Hypofunction
Hypofunction:
- Diabetes Insipidus ( deficiency in ADH)
Etiology (cause):
- Neurogenic
- Nephrogenic
- Psychogenic
- Drug-induced
- Inability to concentrate Urine
- Decreased water reabsoption in kidney
– Decreased Blood Volume, Pressure
– Increased serum electrolytes (Na+: thirst, tachycardia, lethargy, dehydration, thirst, tachycardia, lethargy, dehydration, disorientation, weakness, irritability, muscle twitching)
Dysfunction of the Posterior Pituitary
Hyperfunction
Hyperfunction
- Syndrome of inappropriate ADH secretion (SIADH)
Etiology (cause)
- Neoplasms
- Surgery
- Disease States
- Psychiatric
- Drug-induced
Pathophysiology of SIADH
- ADH continuously released,
– BP, BV increase- BP, BV increase
Hyponatremia (lethargy and confusionlethargy and confusion)
Dysfunction of the Anterior Pituitary
Hypofunction
Hypopituitarism
- Cortisol Deficiency (ACTH), Thyroid deficiency (TSH), Gonadal failure, Loss of 2 sex characteristics(LH, FSH), growth deficiency (GH)
Etiology:
- Primary: Intrinsic pituitary disease
- Secondary: Hypothalamic disorders
- Functional: Anorexia, Chronic starvation
Pathophysiology of Anterior Pituitary
hypofunction
TSH deficiency: Loss of Thyroid hormone production
LH, FSH deficiency
GH deficiency GH deficiency
ACTH deficiency: Loss of adrenal hormone production
- Life threatening; need to immediately intervine
If Brain Injury Patient
You should make a G,T,A study
- To make sure everything is okay and intervine right away
Dysfunction of the Anterior Pituitary
Hyperfunction
Hyperpituitarism
Etiology:
- Pituitary adenoma (secretory)
Pathophysiology: Compression Brain injury
- Hypersecretion of Anterior Pituitary hormones
– Prolactin Prolactin
– GH- GH
– ACTH
Acromegaly
- Decreased life expectancy
- Cardiovascular disease
- Diabetes
- Arthropathy
- Neuropathy
Thyroid gland
Thyroxine (T4) and triiodothyronine (T3):
- Key regulators of metabolism and development and are known to have pleiotropic effects in many different organs
– Increase level of body metabolism
– Regulator of cardiovascular functions
- T4 is the major product
- T3 is most potent/best measure of hyperthyroidism
Calcitonin
- Promotes deposition of calcium in the bones (decreases circulating Ca++)
Changes in cardiovascular hemodynamics is associated with thyroid dysfunction
Check Screen Shot
Alterations of Thyroid Function
Hyperthyroid Conditions
- Graves Disease
- Diffuse toxic goiter
- Drug-induced: excess L-thyroxine administration
Hypothyroid Conditions
- Hypothyroidism
– Primary
– Secondary
- Thyroiditis
– Autoimmune (Hashimoto disease)
– Acute, subacute
Goiter
Can be
- Hyperthyroid
- Euthyroid
-Hypothyroid
Graves’ Disease
Hyperthyroidism; Associated with thyroid enlargement
- Familial disorder
- Occur in youn females (20-40)
- M:1 = 1:7
- Ocular changes with exophthalmos
- Pretibial edema of legs
- Auto-immune etiology
– Stimulatory Thyroid receptor antibodies
- Elevated T4, T3 and depressed TSH
Most common cause of endogenous Most common cause of endogenous hyperthyroidism
check screen shot
Diffuse Toxic Goiter
Induced by stressor
- Irreversible change to follicular cells
- Autonomous function (no feedback control)
– Involution of remaining gland
— Toxic Multinodular goiter
Similar to Graves disease
- but no opthalmopathy, pretibial myxedema
Thyrotoxic crisis
Untreated hyperthyroidism:
- Acute Stressor
– Hyperthermia
– Tachycardia
– Heart failure
– Delirium
– N/V/D
- Chronic untreated effects
High T4/T3 is associated with low TSH (negative feedback)
Hypothyroidism
Primary
- Loss of thyroid tissue (autoimmune)
- Chronic lymphocytic thyroiditis/Hashimoto’s Thyroiditis
Secondary
- Pituitary, hypothalamus disease
- Peripheral resistance to T3/T4
The Major change that happen with Hypothyroidism
The major cardiovascular changes that occur in
hypothyroidism include a decrease in cardiac output and cardiac contractility, a reduction in heart rate, and an increase in peripheral vascular resistance
Hashimoto’s Thyroiditis
(Chronic Lymphocytic Thyroiditis)
- Painless swelling
- In middle aged females (45-65)
- F:M = >10:1
- Caused by TSH-receptor auto antibodies
- Result in gradual onset of hypothyroidism
Hypothyrodism Vs Hyperthyroidism
Screen Shot
DeQuervain disease
- Granulomatous thyroiditis (subacute)
- Patients may initially be hyperthyroid, then Patients may initially be hyperthyroid, then euthyroid.
Prior viral infection has been implicated
Pathophysiologic consequence of chronic dysthyroid states
Cardiovascular disease
- Hyperthyroid states: Atrial Fibrillation (AF), cand it’s cardiovascular Disease
- Hypothyroid states: ↑ cholesterol, Hypertension, atherosclerosis
Thyroid hormone excess on bone metabolism
- Higher osteoporosis risk in people with overt and subclinical thyrotoxicosis.
CNS effect
- Fetal neurodevelopment, neuropsychiatric morbidit (adult)
Thyroid dysfunction and its previous treatment have been implicated in the development of cancers
- Potential carcinogenic effect of radioiodine therapy in the treatment of hyperthyroidism.
Thyroid nodules
Very Common (8% population)
- Increase in incidence with age
- 50% of patients are over 50
- 95% are benign
Thyroid Cancer
Most common endocrine related cancer
- 3.6% of all new diagnosed cancer in U.S
- 60% of thyroid cancer are diagnosed while cancer in primary site
- 25% diagnosed after spread to regional lymph (beyond primary site)
- 5% are diagnosed after cancer metastasized
The incidence of thyroid cancer in females is > 3 times that of males
- Delay in primary treatment Increase probability of thyroid cancer death 2.4 fold
When should one use ultrasound (US) and fine needle aspiration (FNA) in thyroid nodule evaluation?
Assessment of Thyroid Nodules
US examination indicated if a nodule or goiter is palpable and In patients WITHOUT palpable lesions who are at high rish of thyroid cancer
- FNA BIOPSY recognized as Diagnostic procedure of choice (clinically or incidentally discovered thyroid nodules)
Which laboratory evaluations should be performed for thyroid nodules?
If there is no specific clinical suspect; The initial thyroid laboratory evaluation requires the determinatin of TSH ONLY
- Serum Calcitonin (MTC)
Thyroid Cancer
Adenoma (up to 50% of solitary neoplastic nodules)
Carcinoma most common endocrine malignancy
- Papillary adenocarcinoma (65%)
- Follicular Carcinoma (25%)
- Medullary carcinoma- parafollicular cell (MTC; 5-10%)
– Originates from the parafollicular C (calcitonin producing) cells
- Anaplastic carcinoma (10-15%):
– Exxtremely poor prognosis: lethal
– fine needle aspiration biopsy of the mass shows malignant spindle-shaped cells that demonstrate a p53 mutation
Chharacteristics of Papillary Thyroid Cancer
Peak onset 30-50: 3:1 (F:M)
- Prognosis related to tumor size
- 85% of thyroid cancer from radiation
- Metastasis to neck lymph nodes
- Distant spread is uncommon
- Cure rate is high
Characteristics of Follicular Thyroid Cancer
Peak onset 40-69: 3:1 (F:M)
- Prognosis is related to tumor size
- Spread to lymph nodes is uncommon
- VASCULAR invasion is Common
- Cure rate is high in young: lower with higher age
Adrenals
Outer Cortex:
Aldosterone (Mineralocorticoids)
- Sodium and fluid retention, resulting in ↑ in intravascular volume.
- Produced in Zona glomerulosa
Cortisol (Glucocorticoids)
- Multiple metabolic functions for the control of protein, carbohydrate, fat metabolism
- Produced in the Zone Fascicularis
Sex Androgens:
- Produced in the Zona Reticularis
Inner Medulla:
Norepinephrine/Epinephrine/Dopamine
- Increase BP, CNS Stimulation
Cushining’s Syndrome
Adrenal Hyperfunction:
- Central Obesity (rapid weight gain to the face, neck and trunk, but sparing the extremities)
– Associated with kyphosis, amenorrhea or impotence, hypertension, and extreme weakness
- Hyperglycemia
- Hypertension
- Continued presence of Cortisol levels (promotes obesity)
- Ecchymoses
- Thinner hair
- Moon face, and ruddy complexion
- Mood swings
Pituitary Tumors
Most common
- Increased serum ACTH (pituitary tumor) => Increased cortisol (enlarged adrenal cortex)
- Feedback infeffective
Adrenal Cortex Tumor
Increased Serum Cortisol => Inhibit ACTH secretion (through feedback to the pituitary)
- THis mean we will have an increase in Cortisol and a decrease in the ACTH
Paraneoplastic Syndrome
Increased serum ACTH and cortisol
- Lung Cancer (increased ACTH seccretion) => Enlarged Adrenal cortex => Increased cortisol secretion
Iatrogenic
Increased Cortisol and decreased ACTH
Ingest Cortisol medication => Inhibit hypothalamic pituitary ACTH secretion => Adrenal Cortex atrophy => NO CORTISOL SECRETION
Addisons Disease
Primary hypocortisolism
Increase in ACTH with inadequate corticosteroid synthesis
- diopathic organ-specific autoimmune etiology
– Destruction of adrenals: tuberculosis, trauma, etc.
- Women 30-60 years of age
Clincal Signs
- Weakness, N/V, GI disturbances, Hyperpigmentation
- Hypoglycemia-decr. Gluconeogenesis
- Recall CRH is CO-SECRETED with ADH: feedback control (Hyponatremia)
Addisons Disease
Waterhouse-Friderichsen syndrome
Meningococcemia: Acute infection with Neisseria meningitidis can produce can produce this form of acute adrenal failure
- Petecbial rash, coagulopathy, Cardiovascular collapse, Bilateral adrenal hemorrhage
- Cases of purpura fulminans, cutaneous ecchymosis, hypotension, and fever in patients for whom the culture data are unknown classified as probable
meningococcemia.
Adrenals-Aldosterone
Aldosterone
Deficiency: Hypoaldosteronism
- Hyperkalemia (high K+)
– Signs: abdominal cramping, fatigue, lethargy, and muscle weakness
– Sever Hyperkalemia will slow cardiac impulse conduction producing classic ECG changes
- Hypotension (low BP)
Excess: Conn’s syndrome
- Hypertension, Hypokalemia
- Resistant Hypertension
Aldosterone
Mech: Excess
Binding of aldosterrone receptor to mineralcoricoid response element
- Increase transcription of gene encoding aldosterone inducible proteins
– Apica epithelial sodium channel (ENaC)
– Basolateral sodium potassium (Na/K) ATPase
This stimulate sodium (NA+) reabsorption and potassium (K+) excretion
- Hypokalemia, Hypertension
Resistant Hypertension
Blood pressure that remain higher than normal despite the use of 3 antihypertensive medication
- They are at disproportionately high risk for target organ damage and cardiovascular events
- Associated with: Older age, more sever hypertention, chronic kidney disease, femal sex, black race, obesity, and diabetes
Recent studies indicate that primary aldosteronism is a common caus eof resistant hypertensio (2-20% prevalence)
Challenges in Endocrine Pathophysiology
Early detection
Sensitive and specific accessible biomarkers
Coordinated multidisciplinary endocrine pathophysiology health care delivery support
Suspected Increasing incidence of endocrine diseases
- Neoplastic, Autoimmune, Drug-induced
Familial/genetic relationship
- Monogenetic/polygenetic: in dysfunction and neoplastic disease progression
- Morphology-genotype correlation
