Endocrine Flashcards
What is the role of endocrine glands?
To release chemical messengers directly into the bloodstream
Three different types of chemical hormones
o Peptide hormones
o Amino acid derived hormones
o Steroid hormones
Effectiveness of a hormone depends on whether the hormone is (2)
FREE and BIOLOGICALLY AVAILABLE
What do we mean when we say that a hormone needs to be “free”?
We mean “not bound to a plasma protein.” (which lipid soluble vitamins need to do to travel in the blood
What do we mean when we say that a hormone needs to be “biologically available”?
- Activation may occur in bloodstream, eg angiotensinogen → interacts with rennin to become angiotensin I → ACE
- Activation may be carried out by the liver
What is hormonal regulation? Depends on…
o Rate of absorption of hormone (drain)
o Rate of elimination of hormone (faucet)
How does hormonal feedback regulation work?
Negative feedback system to original gland
What is the role of specific hormone binding proteins?
o Help facilitate the hormone’s tendency toward creating long term actions (extends half-life)
Two locations of hormone receptors
o Surface receptors on the membrane (Second messenger system involved)
o In the nucleus – on the promoter region (typical of steroid hormones)
Sources of alterations in endocrine function (6)
- Hormone secretion
- Less Hormone Binding → Higher concentration of free hormone
- Altered rate of elimination: Liver or Kidney problems
- “Hormone Resistant Conditions”: Failure of target cell to respond to hormone:
- Autoimmune problem with endocrine cell = primary deficiency of that hormone
- Pituitary Gland and Alterations in Function
What may cause a hypersecretory problem (hormones) (2)
- May be due to adenoma – overgrowth of endocrine tissue
* Ectopic production: Cancer cells may oversecrete hormones –>No feedback regulation
What may cause less hormone binding?
o May be caused by liver problem, plasma protein / albumin deficiency
o Affects rate at which the hormone binds to the target cell, gets eliminated.
What may cause altered rate of elimination?
o Liver or kidney problems: Some hormones need to be biotransformed by liver, excreted by kidneys
What occurs in “hormone resistant conditions?” Which is the most common?
Target cell fails to respond to hormone.
Three types of hormone resistant conditions. Which is the most common?
- **Receptor associated disorders
- Intracellular disorders
- Feedback regulation becomes altered
(Receptor associated disorders = most common)
What occurs with receptor associated disorders? What type of hormone does this most often happen to?
- Rate of receptor expression may be decreased or sensitivity decreased
- Mostly lipid soluble hormones
Two examples of autoimmune problems with endocrine cells.
What occurs?
o Diabetes mellitus Type 1
o Hashimoto Thyroiditis (Hypothyroidism)
Primary deficiency of that hormone
Alterations to the pituitary gland: Posterior lobe
- How common?
- How is this associated with the hypothalamus?
- What are the cell types?
- What are the hormones produced? (2)
- 10% of pituitary masses?
- Neurological extension of the hypothalamus
- Axon terminals of the neurosecretory neurons in the PVN and SON of the hypothalamus
- Vasopressin (ADH), Oxytocin
Alterations to the pituitary gland: Anterior lobe
- How common?
- How is this associated with the hypothalamus?
- What are the cell types?
- What are the hormones produced? (2)
- 90% of pituitary masses
- Hypothalamic tropic hormones act on these cells to stimulate other hormone release
- Contains glandular cells arranged in nests surrounded by dense vascular tissue
What are the hypothalmic tropic hormones (5)? What is their role?
- Corticotropes – secrete ACTH
- Lactotropes – secrete prolactin
- Somatotropes – secrete GH – constitute half of all hormone-producing cells in the anterior lobe
- Thyrotropes – secrete TSH (5% of all cells in the AP)
- Gonadotropes – secrete FSH and LH
(All stimulate endocrine glands except prolactin – stimulates excretory gland)
What are 2 examples of a hypersecretory disease of the posterior pituitary?
- Syndrome of Inappropriate ADH secretion (SIADH)
- Diabetes insipidus
What is SIADH? Def
Syndrome of Inappropriate ADH:
- High levels of ADH in the absence of normal ADH secretion stimuli
What happens to osmolarity with SIADH? What happens to urine?
ADH levels are high, plasma osmolarity low (dilute): TOO MUCH WATER RETAINED, urine very concentrated.
SIADH: Causes (6)
- Increased hypothalamic production
- Pulmonary diseases
- Severe nausea and/or pain
- Ectopic production of AHD
- Drug induced potentiation of AHD
- Idiopathic
What can cause increased hypothalamic production (ultimately resulting in SIADH)?
- Infections (meningitis, encephalitis, etc)
- Neoplasms
- Drug-induced (chemotherapeutics, antipsychotics)
What pulmonary diseases can result in SIADH (4)?
What is the mechanism?
- Pneumonia
- Tuberculosis
- Acute Respiratory Failure (ARF)
- Asthma
**Mechanism unclear; could be compensatory
Why would severe nausea and/ or pain trigger SIADH?
Due to SNS stimulation, which triggers ADH
3 ectopic causes of SIADH
- Small cell / oat cell carcinoma of the lungs
- Bronchogenic carcinoma
- Carcinoma of duodenum
Clinical manifestations of SIADH (2)
(1) Serum hypoosmolarity and natremia
(2) Urine hyperosmolarity
What are three other clinical manifestations of SIADH (noted to r/o other disorders)?
(1) Urine sodium excretion matches sodium intake
(2) Normal adrenal and thyroid function
(3) Absence of conditions that can alter volume status (Coagulative heart failure, Renal insufficiency)
Four distinct types of osmolaregulatory defects and their prevalence (%)
TYPE A: Random (20%)
TYPE B: Osmostat reset (~35%)
TYPE C: Leak (35%)
TYPE D: renal insensitivity (10%)
Describe what occurs in Type A osmoregulatory Disorders
RANDOM
Large and unrelated fluctuations in ADH (aka AVP) occur unrelated to the rise of plasma osmolarity
Describe what occurs in Type B osmoregulatory Disorders
OSMOSTAT RESET
Prompt and parallel rise in AVP with plasma osmolarity, but a significant lowering of the threshold for release is present
Describe what happens in Type C osmoregulatory disorders
LEAK
ADH (AVP) is persistently elevated at low and normal plasma osmolarity. Above the threshold for AVP release, AVP increases normally.
Describe what occurs in Type D osmoregulatory Disorders
RENAL INSENSITIVITY
Plasma ADH (AVP) is appropriately suppressed under hypotonic conditions and does not rise until plasma osmolarity reaches the normal threshold level—it does not result in maximal urinary dilution.
Type A Pattern
Usually occurs in association with tumors
Type B Pattern
Consistent with an osmoreceptor reset at a lower-than-normal level (pulmonary disorders)
Type C Pattern
Observed in meningitis, head injuries
Type D Pattern
Consistent with an increased renal sensitivity to vasopressin
Treatments for osmoregulatory defects (2)
- Fluid restriction
- V2 (vasopressin) receptor blockers
Diabetes insipidus is characterized by what?
The excretion of large volumes of dilute urine, having nothing to do with plasma glucose
What are the two types of Diabetes Insipidus?
- Neurogenic (or central): Failure to produce ADH
* Nephrogenic (renal): Failure to respond to ADH
What is the most common cause of DI at all ages?
Destructive lesions of the pituitary and/or hypothalamus
What causes neurogenic diabetes insipidus (3)
- Head trauma
- Tumor
- Neurosurgical procedures
What is going on genetically with nephrogenic diabetes insipidus?
Type of Inheritance
- CDI with an autosomal dominant pattern inheritance
What three disorders may be linked to an autosomal recessive pattern associated with Diabetes Insipidus?
- Diabetes Mellitus
- Optic atrophy
- Mental retardation (Wolfram syndrome)
What is going on genetically with nephrogenic diabetes insipidus?
Mutation of what gene? (name 4…?!)
- Due to a mutation in the prepro-arginine vasopressin (prepro-AVP2) gene
- X-linked NDI occurs from mutations in the antidiuretic arginine vasopressin V2 receptor (AVPR2) gene, mapped to Xq28
• NDI with an autosomal dominant recessive pattern is due to mutations in the gene designated to AQP2; this gene directs water channel formation in the distal tubule.
Clinical manifestations of DI
- Polyuria:
* Polydipsia
Polyuria in diabetes insipidus
2 characteristics
- Massive amount of dilute urine (little to no ability to concentrate urine = plasma osmolarity 500 mOsms)
- Insipidus = “without taste” (in DM, urine tasted sweet)
Why does a DI patient suffer polydipsia?
• Extreme thirst, because plasma is always hyperosmolar
How do the lab values for Diabetes Insipidus compare to the lab values of SIADH?
MIRROR IMAGE.
In DI, plasma osmolarity is concentrated / urine osmolarity is dilute (low specific gravity)
What type of Diabetes insipidus is easier to treat? Why?
Central DI is easier to treat
For Central DI, just administer synthetic ADH. For Nephrogenic DI, Kidney is no more sensitive to synthetic ADH than it is to natural ADH
Treatment for central DI
Administer synthetic ADH
Treatment for Nephrogenic DI
- Restrict physical activities to prevent water loss
- Vigilant hydration
- Paradoxically, thioside diuretics can be used for tx
Why are thyoside diuretics an effective treatment for nephrogenic DI?
Increases sodium loss → Decreases hypernatremia
Diseases of the anterior pituitary (3)
- Hypopituitarism
- Hyperpituitarism
- Hypersecretion of GH
What do adenomas of pituitary cells cause?
Can cause either hypo- or hyper- thyroidism
Either crushes the gland or causes hypersecretion
What is panhypopituitarism?
A total failure of pituitary function.
What can cause disorders of the anterior pituitary? (7)
- Adenomas (Pituitary Tumors)
- Sheehan Syndrome:
- Iatrogenic Hypopituitarism
- Trauma
- Infiltrative Diseases
- Genetic Abnormalities of Pituitary Development
- Growth Hormone Insensitivity: Laron Syndrome
How can an adenoma cause hypopituitarism in the anterior pituitary?
• Pituitary adenoma crushes pituitary gland against the turca selcia (Bone) → Causes injury to secretory cells → Decline in pituitary secretions.
How can Sheehan syndrome cause hypopituitarism in the anterior pituitary?
• During pregnancy, pituitary gland bulks up → Increased oxygen demands → Becomes vulnerable to ischemia → Ischemic damage occurs with hemmhorage
What is Sheehan Syndrome?
A complication of postpartum hemmorhage
When might an iatrogenic hypopituitarism occur?
- Inadvertently caused by medical intervention
* Due to neurological surgery that causes direct damage or increased ICP
What is an example of an infiltrative disease that might cause hypopituitarism?
Meningitis
What is Laron Syndrome?
- Physiologically
- Clinically. Why?
Primary insensitivity to growth hormone: Adequate GH is produced, but GH receptors are impaired.
Result: Person has proportional body, but small stature. B/c growth hormone is necessary for bone elongation
How are pituitary adenomas classified? List (3)
According to their staining properties
• Acidophil
• Basophil
• Chromophobe
Acidophil pituitary adenoma: effects on endocrine function (2)
- Associated with oversecretion of GH
- Now more regularly classified by what they secrete
Basophil pituitary adenoma: effects on endocrine function
– associated with oversecretion of ACTH
Chromophobe pituitary adenoma: effects on endocrine function
– no endocrine hyperfunction
How does size impact the effect of pituitary adenomas?
- Adenomas less than 10mm in diameter (microadenomas) do not cause symptoms unless they produce hormone
- Larger Pas (macroadenomas) cause local symptoms (impinging on other structures) and systemic symptoms b/c of hormone oversecretion
Types of pituitary adenomas (5)
Which is the most common?
- Lactotrope Adenoma (prolactinomas) –> most common
- Somatotrope adenomas
- Corticotrope Adenoma
- Gonadotrope Adenoma
- Thyrotrope Adenomas
Types of nonfuncitonal pituitary adenomas (3)
- Null cell adenomas
- Oncocytoma
- Silent Adenomas
• ___% of all pit tumors removed surgically do not secrete excess hormone
25
What are null cell adenomas?
o Chromophobic cells that test negative for all hormones
What are oncocytomas?
o Similar to null cell but with higher mitochondrial density
What are silent adenomas?
o Test positive for ACTH and sometimes other hormones as well – but never secretory
Macroadenomas: Symptoms (4)
- Visual disturbances, blurry vision, loss of parts of the field of vision
- Headaches (chronic)
- Increased ICP → Seizure
- Impinge on hypothalamus → Problems with regulating bladder function, temp, plasma osmolarity
Hypersecretion of growth hormone: Clinical manifestation (2)
- Acromegaly in adults
- Gigantism in children
Why are the clinical manifestations of excess GH different for children verses adults?
• Cartilage epiphysis seals off at puberty (because of sex hormones)
Characteristics of a patient with acromegaly (6)
- Increase in soft tissue: Enlarged hands, feet, nose, lips, ears.
- Skin will seem much thicker
- Pronounced brow ridges
- Thick, protruding lower jaw (teeth of lower jaw look like they have gaps)
- Enlargement of some internal structures (cardiomegaly – decreases contractility)
- Thickening of vocal cords (very deep voice)
Metabolic effects of excess GH (4)
- Increased metabolic rate
- Hyperglycemia from GH inhibition of glucose uptake in peripheral tissue
- Increased hepatic production of glucose
- This often leads to a compensatory hyperinsulinism and finally insulin resistance (DM2)
What else increases with GH?
Insulin-like growth factor
Complication of Hypersecretion of GH
Macro adenomas
Treatment for hypersecretion of GH
OCTRIOTIDE
A somatostatin; decreases GH production
Diseases of the thyroid gland (3)
- Nontoxic goiter: Euthyroidism
- Hypothyroidism (Hashimoto Thyroiditis)
- Hyperthyroidism (Grave’s)
Diseases of the adrenal cortex (3)
- Congenital adrenal hyperplasia (CAH)
- Adrenal cortical insufficiency (Addison)
- Adrenal hyperfunction (Cushing)
Define “Nontoxi goiter” / euthyroidism
The capacity of the thyroid to produce thyroid hormone (T3 and T4) is impaired / inefficient, so the body compensates by increasing TSH
Elevated levels of TSH cause…
- Normal T3 and T4
- Enlarged thyroid gland
What is a nontoxic goiter in the early stages of the disease? Describe
DIFFUSE NONTOXIC GOITER
- Gland is diffusely enlarged
- Microscopically exhibits hypertrophy and hyperplasia of the epithelial follicular cells
What is a nontoxic goiter as the disease evolves?
MULTINODULAR NONTOXIC GOITER
Can become a toxic goiter, which would be hypo/hyperthyroidism with a goiter
Hypothyroidism is a consequence of what three general processes?
(1) Defective synthesis of thyroid hormone (with compensatory giotrogenesis)
(2) Inadequate function of thyroid parenchyma
(3) Inadequate secretion of TSH – by pituitary or of TRH by hypothalamus
what causes inadequate function of thyroid parenchyma
usually a result of thyroiditis or surgical resection of the gland or the therapeutic administration of radioiodine
What is the most common cause of primary hypothyroidism?
AUTOIMMUNE (Hashimoto thyroiditis)
What happens in Hashimoto Thyroiditis?
- Autoimmune destruction of thyrocytes (thyroid gland cells)
- Both t-cell initiated destructino adn antibody-initiated destruction
- High TSH, High TRH
Possible causes of primary hypothyroidism (8)
- Autoimmune
- Postradioactive
- Thyroidectomy (total or subtotal)
- Radiation therapy for head / neck cancers and lymphomas
- Iodine deficiency
- Congenital disorders of thyroid hormone synthesis
- Iodine excesses
- Certain drugs
What drugs might cause hypothyroidism?
- Lithium – used to treat bipolar
- Interferon alpha – abx
- Some antiepileptic drugs
- What is Mike’s edema?
- What disease process is it concurrent with?
- A non-pitting edema
- Hashimoto thyroiditis
Mike’s Edema: Physiology
Accumulation of mucopolysaccharides attached to the extracellular matrix of tissues
Mike’s edema: Clinical manifestations (5)
- Enlargement in tongue, hands, tibial region (shin)
- Appears like red bumpy plaques on skin
- Puffiness in face
- May enlarge heart
- Altered mental status = Mike’s edema Madness
Clinical manifestations of hypothyroidism
- Fatigue
- Feel cold + Cold extremities
- Poor memory / concentration
- Weight gain
- Shortness of breath
- Hoarse voice
- Impaired hearing
- Skin: Dry and coarse
- Carpel tunnnel
- Mike’s Edema
- 3rd space fluid accumulation
- Prolonged menstrual cycles
- Goiter
Why would a hypothyroid patient experience a goiter?
Excess TSH
Signs and symptoms of hyperthyroidism reflect a _______ state
HYPERETABOLIC
General causes of hyperthyroidism. Which is the most common?
(1) Presence of abnormal thyroid stimulator (graves disease)
(2) Intrinsic disease if the thyroid gland (toxic multinodular goiter or functional adenoma)
(3) Excess production of TSH by anterior pituitary (rare)
GRAVE’S is most common
Mechanism of Grave’s (general)
Body produces an immunoglobulin antibody that attaches to the TSH receptor and acts as an antagonist to that receptor (activates it)
Mechanism of Grave’s (more specific)
- What is stimulated?
- What is produced?
- what is the result? (2)
o Ig antibody stimulates both thyroid hormone production and enlargement of the thyroid gland
o Immune system produces TSH agonist → High T3 & T4
o Because of elevated T3 and T4, less TRH and TSH are being produced
o Immune system is not part of regulatory loop; keeps stimulating the thyroid gland.
Clinical manifestation of hyperthyroidism
- Goiter
- Exophthalamos: Extreme eye bulging (Due to retro-orbital swelling)
- Irritable
- Nervous
- Jittery, constantly moving
- Hand tremors
- Difficulty sleeping
- Thin looks thin and delicate
- Weight loss (but good appetite)
- Muscle wasting
- Tachycardia
- Increased sweating
- Amenorhea, or Oligomenorhea (decreased frequency /duration)
What hormones does the adrenal cortex produce? (Hint: This is review)
3 categories
1) Glucocorticoids
2) Mineral corticoids (Aldosterone)
3) Sex hormones
What are the three types of glucocorticoids?
Cortisol
Cortisone
Corticosterone
Of the adrenal hormones, which is the most devistating to lack?
Aldosterone
Name 4 sex hormones
- Androgens
- Testosterone
- Estrogen
- Progesterone
What causes Congenital Adrenal Hyperplasia (generally)?
- A number of autosomal recessive enzymatic defects in the biosynthesis of cortisol from cholesterol
A deficiency of ________ (enzyme) is responsible for ___% of CAH cases.
21-hydroxylase
90%
What does a deficiency in 21-hydrogenase cause…
- Chemically?
- Physically? (2)
- Diagnosis?
- Causes lack of cortisol and the buildup of intermediates / increased production of androgens
- Ambiguous genitalia is a direct result of the excess intermediates
- Hyperplasia = a consequence of the lack of cortisol
DIAGNOSIS: CONGENITAL ADRENAL HYPERPLASIA
Clinical manfestations of Congenital Adrenal Hyperplasia (not genitalia) - 2
• Small kidneys, massive adrenal glands (Hyperplasia due to lack of cortisol)
o Cortisol provides negative feedback to:
- The pituaitary gland and its production of ACTH.
* The hypothalamus and its production of CRH
CAH: Affect on female genitalia
- Exhibit pseudohermaphroditism (due to increased masculinization of genitalia in utero)
- Fusion of the labia, an enlargement of the clitoris, shortened vaginal canal.
1 cause of ambiguous genitalia in girls
CAH due to buildup of intermediates and an increased production of androgens
CAH: Affect on male genitalia
- Exhibit no abnormalities of the sexual organs
* May experience sexual precocity, stunted growth
What is Addison’s disease?
- Adrenocortical insufficiency due to the destruction or dysfunction of the entire adrenal cortex.
- Primary autoimmune destruction of adrenal tissue
What hormones does Addison’s disease affect?
• Affects both glucocorticoid and mineralocorticoid function.
Adrenal cortical insufficiency (Addison’s): Clinical manifestations
- Hyperpigmentation
- Progressive weakness, severe chronic fatigue
- Decreased GI function: Poor appetite, weight loss / difficulty maintaining weight
- Chronic Hypotension
What causes the hyperpigmentation in addison’s patients?
Excess ACTH on melanocytes
Why do Addison’s patients experience chronic hypotension?
cortisol usually provides baseline tone to the vasculature; aldosterone helps maintain blood volume.
• Therefore, deficiencies lead to decreased tone, decreased blood volume.
Blood levels in Addison’s (3)
- Hyponatremia
- Hyperkalemia
- Hypoglacemic
What is a severe complication of Adrenal Cortical Insufficiency?
In absence of adrenal cortex hormones, YOU CANNOT MOUNT AN ADEQUATE STRESS RESPONSE. Therefore, physical stress results in hypotension, shock, and risk of death.
Cushing’s Syndrome: Cause (general)
Prolonged exposure to elevated levels of either endogenous glucocorticoids or exogenous glucocorticoids.
Who is most susceptible to Cushing’s?
Women
Cushing’s Syndrome: Cause (specific) - 4
o Exogenous steroid administration
o Endogenous glucocorticoid overproduction
o Primary adrenal lesions
o Ectopic ACTH production
What patient would receive steroids? (3)
- Patients with autoimmune disoders
- Asthma
- Transplant patients
What would cause endogenous glucocorticoid overproduction?
ACTH-producing pituitary adenoma (rare)
What would cause ectopic ACTH production? What in particular is implicated?
- Tumors outside of pituitary gland
* Lung cancers particularly implicated
Clinical manifestations of Cushing’s (11)
o Increases subcutaneous fat
o Decreases subcutaneous fat
o Face may be flushed
o Increases cognitive and emotional excitability
o Bone demineralization / bone breakdown
o Hyperglycemia
o Electrolyte imbalances
o Hypertensive
o Ovulatory dysfunction
o In females – excess facial hair
o Breakdown in skin integrity
3 places a Cushing’s patient would experience increased fat:
Subcutaneously:
• In face (moon face)
• Between shoulder blades (buffalo hump)
• In middle of body (also nonsubq fat here)
Electrolyte imbalances in a Cushing’s patient
- Retention of sodium
* Loss of potassium
Changes in vasculature with a Cushing’s patient
- Vasoconstriction
* Left ventricular hypertrophy
Changes in females with Cushing’s (2)
- Amenorrhea
* Excess facial hair
