What produces releasing hormones?
What releases stimulating hormones?
Releasing= hypothalamus
Stimulating= pituitary
Thyroid hormone releasing hormone (THRH) stimulates the thyrotroph cells of the ______ pituitary to release thyroid-stimulating hormone (TSH)
ANTERIOR pituitary
TSH stimulates the thyroid gland to release…
T4 and T3
The prolactin system is what kind of a system?
Inhibitory!
Hypothalamic dopamine inhibits ______ release from the anterior pituitary
Prolactin
ADH
Oxytocin
..are released from which part of the pituitary?
Posterior pituitary
GH
TSH
Prolactin
ACTH
FSH
LH
Released from anterior pituitary
thyroid hormone (T4 and T3) exerts negative feedback on….
hypothalamus and pituitary
in a primary hyper- disorder….
the concentration of the hormone secreted by the target gland will be _________
the stimulating hormone concentration (from the pituitary) will be ________
hormone secretion HIGH*
stimulating hormone will be LOW* (due to negative feedback from hyperactive target gland)
A primary disorder suggests an issue in the…
target gland!
The pituitary/hypothalamus over stimulates the target gland
..what kind of disorder?
a secondary disorder
In a secondary hyper-disorder
What will the target gland hormone levels look like?
What will the stimulating hormone levels look like?
BOTH target gland hormone and stimulating hormone levels will be high!
A struma ovarii (ovarian tumor) can secrete ectopic….
TSH
Small cell lung cancer can ectopically produce..
ACTH
Squamous cell carcinoma of the lung can secrete (ectopically)…
Parathyroid hormone-related protein (PTHrP)
If the target hormone receptors are hyperactive (ie genetic mutation)…what can happen to hormone secretion?
Increased!
hyper- condition
In a primary hypo-disorder
Target hormone level?
Stimulating hormone level?
LOW target hormone levels
HIGH stimulating hormone levels (trying to bring up the target hormone levels)
In a secondary hypo- disorder
Target hormone level?
Stimulating hormone level?
BOTH DECREASED
The hypothalamus does not secrete enough releasing hormone
tertiary disorder
Prolactin is inhibited by..
Dopamine
A toxic thyroid nodule
Grave’s Disease
Pituitary tumor
Amiodarone toxicitiy
Struma ovarii
HYPERthyroidism
How do you distinguish whether HYPERthyroidism is due to a primary or secondary cause?
TSH levels!
TSH levels in primary hyperthyroidism
LOW!
(
TSH levels in secondary hyperthyroidism
HIGH
A thyroid nodule that becomes dependent of the pituitary and secretes excess thyroid hormone
Toxic nodule
Autoimmune disorder that causes HYPERthyroidism
*autoantibodies bind to the TSH receptors in the thyroid and act just like TSH, stimulating the thyroid to release thryoid hormone (T3/T4)
Grave’s disease
MC cause of hyperthryoidism?
Grave’s disease
Inflammation of extraocular muscles and periorbital tissue leading to bulging of the eyes, called proptosis or exophthalmos
Grave’s ophthalmopathy
Pretibial myxedema
Non pitting edema on anterior knee
*seen in Grave’s disease
Is Grave’s disease associated with other autoimmune disorders?
It can be!
ie.. vitiligo, pernicious anemia
Amioadrone toxicity can cause…
HYPERthyroidism
High metabolism (weight loss)
Tachycardia (a fib)
Dyspnea
Heat intolerance
Hot skin
Increased appetite
Tremor
Nervousness
HYPERthyroidism
Ophthalmopathy
Pretibial myxedema
Diffuse goiter and/or thyroid bruit
…will point towards a diagnosis of?
Grave’s disease
(HYPERthyroidism)
TSH will be low in what type of hyperthyroidism
Primary!
(TSH will be high in secondary hyperthyroidism)
anti-TSH receptor antibodies can be found in serum in many (but not all) cases of….
Grave’s disease
Which drug class can be used to tx tachycardia, anxiety, etc. associated with hyperthyroidism
Beta blockers
Beta blockers are typically used in cases where teh hyperthyroidism will…..
resolve spontaneously (ie thyroiditis)
Methimazole
Propylthiouricil
both of these drugs decrease..
Thyroid hormone synthesis
(propylthiouricil also reduces peripheral T4 and T3 conversion)
Surgical removal of thyroid
Destroyed thyroid with radioactive iodine (I-131)
can be used in the tx in..
Hyperthyroidism
TSH levels in primary HYPOthyroidism
High!
TSH levels in secondary HYPOthyroidism
Low
Congenital thyroid problems
Hashimoto’s thyroiditis
Drugs that are toxic to thyroid (ie amiodarone)
Iodine deficiency
Radiotherapy with I-131
…all causes of?
Primary Hypothyroidism
An autoimmune disease that causes primary hypothyroidism
Antibodies are directed against thyroid peroxidase (TPO) and thyroglobulin (TG), resulting in a lymphocyte infiltration of the thyroid gland. this causes the thyroid gland to cease functioning partially or entirely
Hashimoto’s thyroiditis
Sometimes occurs with other autoimmune disease (ie diabetes Type 1, vitiligo, prematurely greying hair)
Hashimoto’s thyroiditis
Why does iodine deficiency cause hypothyroidism?
Iodine is necessary for thyroid hormone synthesis
Weight gain
Cold intolerance
Fatigue
Weakness
Bradycardia
Hypoventilation
Constipation
Myalgias
Arthralgias
Anemia
Goiter may be present
HYPOthyroidism
Serum autoantibodies (anti-TPO and anti-TG) can be present in…
Hashimoto’s thyroiditis
Thyroxine, a synthetic form of T4, is used in the tx of?
Hypothyroidism
Inflammation of the thyroid gland
Can cause hyperthyroidism or hypothyroidism
Thyroiditis
Causes include:
Viral infection (de Quervain’s)
Radiation
Amiodarone
Autoimmunity
Delivery of a baby
Thyroiditis
Can be neoplasms:
*Adenoma (benign)
*Carcinoma (papillary, follicular, medullary, anaplastic)
Can be non-neoplastic:
*Cyst
*Hyperplasia
*Focal thyroiditis
Thyroid nodules
How do you diagnose the type of thyroid nodule?
Fine needle aspiration
Which layer of the adrenal cortex secretes aldosterone?
Zona glomerulosa
Which layer of the adrenal cortex secretes glucocorticoids?
Zona fasciculata
Which layer of the adrenal cortex secretes sex hormones?
Zona reticularis
What part of the adrenal gland secretes epinepherine?
Adrenal medulla
What causes…
Reabsorption of sodium (Na+)
Secretion of potassium (K+) and hydrogen ions (H+) in the kidneys
Aldosterone
Renin-Angiotensin
Hyperkalemia
Hyponatremia
Hypotension
..increase/decrease aldosterone secretion?
Increase!
Stress response hormones
- *Increase** BP
- *Increase** gluconeogenesis
- *Decrease** immune response
Glucocorticoids
ie..Cortisol
Clinical manifestation of cortisol elevation
Cushing’s syndrome
Pheochromocytoma occurs in over secretion of…
Epinepherine
What causes sodium reabsorption (which raises BP) and potassium excretion
Aldosterone
Can cause:
Hypernatremia
Hypokalemia
Hypertension
HYPERaldosteronism
What will Renin levels look like in primary HYPERaldosteronism
LOW!
(primary means issue to adrenal gland itself…negative feedback loop on Renin being released from kidneys)
Causes:
- Iatrogenic (long term tx of steroids)
- primary oversecretion by 1 or both adrenal glands (adrenal adenoma or carcinoma)
- overstimulation of adrenal glands by an ACTH-secreting tumor in pituitary
- overstimulation of adrenal gland by ectopic ACTH producing tumor (ie small cell lung cancer)
Cushing’s syndrome
Overstimulation of adrenal glands by an ACTH secreting tumor in pituitary
Cushing’s DISEASE
Truncal obesity
Moon face
Buffalo hump
Easy bruising
Osteoporosis and/or osteonecrosis
Hirsutism
Acne
Cognitive effects (mood changes to psychosis)
Cushing’s syndrome
24-hour urinary collection for free cortisol
Checking level of cortisol in saliva in late evening
Dexamethasone supression test
Ways to test if cortisol levels are high..Cushing’s Syndrome
How do you determine pituitary vs ectopic cause of Cushings?
Dexamethasone Suppression Test
Under normal circumstances, dexamethasone should mimic what?
Cortisol
(which will exert negative feedback on pituitary, decreasing ACTH production)
If a low dose dexamethasone suppression test does NOT suppress ACTH, this indicates…
Cushing syndrome exists
(but does not indicate the source of ACTH over production)
If the pituitary is over secreting ACTH (Cushing’s disease) and you give high dose Dexamethasone, how will the pituitary respond?
Will respond to negative feedback, ACTH level should decrease
*In Cushing’s disease, the pituitary still responds to negative feedback but needs higher levels than normal
Will an ectopic production of ACTH respond to high dose dexamethasone?
NO
Metyrapone inhibits cortisol synthesis and can be used to localize….
Cushing’s syndrome
Metyrapone will do what to ACTH levels in a normal person? in a person with a pituitary tumor (Cushing’s disease)
ACTH levels will be decreased in both
(Metyrapone inhibits cortisol, which will negative feedback decrease ACTH levels)
Pathology of one or both adrenal glands (primary adrenal insufficiency), AKA…
Addison’s disease
Both cortisol and aldosterone secretion are effected in what type of adrenal insufficiency?
Primary
*will have signs/symptoms that reflect both aldosterone and cortisol loss
Addison’s disease is what type of adrenal insufficiency?
Primary
Hypotension
Hyperkalemia
Hyponatremia
Salt craving
Hyperpigmentation
Can be used to distinguish primary adrenal insufficiency from secondary adrenal insufficiency
Polyglandular autoimmune sydrome Type 1 and Type 2
Adrenal hemorrhage
Infection
Tumor metastases
Causes of primary adrenal insufficiency
Lack of ACTH secretion from the pituitary leads to what type of adrenal insufficiency?
Lack of CRH from hypothalamus leads to what type?
Secondary adrenal insufficiency= lack of ACTH
Tertiary adrenal insufficiency= lack of CRH
Rare but dangerous cause of hypertension
*catecholamine secreting tumor that most commonly occurs in the adrenal medulla
causes vasoconstriction, and thus HTN
Pheochromocytoma
Elevated urine levels of catecholamines and their metabolic by-products, metanephrines
Confirm diagnosis of Pheochromocytoma
Dopamine release from the hypothalamus inhibits _______ release from the anterior pituitary
Prolactin
The endocrine cells of the pancreas secrete…
Insulin
Glucagon
*which regulate glucose level
INsulin drives glucose….
INto cells
Causes release of glucose into blood for tissue that need it
(used when no circulating glucose)
Glucagon
A normal blood glucose concentration
Euglycemia
Insulin and glucagon work in concert to maintain….
Euglycemia (normal blood glucose concentration)
When there is lots of glucose around (ie after big meal), insulin is release from….
Beta cells of pancreas
Insulin stimulates glucose uptake into cells and its storage as….
Glycogen (glycogenesis)
Fat
Protein
How is glucose stored?
Glycogen
Biosynthesis of glycogen, the storage form of glucose
Glycogenesis
Glucose breakdown for energy
Glycolysis
Glycogenesis and glycolysis are both stimulated by…
Insulin!
the goal of insulin is to REDUCE BLOOD SUGAR LEVELS, so insulin promotes both glucose storage and breakdown
________ is secreted during a fast when blood sugar is low
Glucagon
________ decreases glycolysis and increases gluconeogenesis (glucose formation) and glycogenolysis (breakdown of glycogen to release glucose)
Glucagon
Goal of _____ is to mobilize glucose stores from the liver so that this glucose can be sent to the brain and heart and used for energy production in those organs
Glucagon
Result from an autoimmune process that destroys the beta cells of the pancreas, leading to loss of insulin production
Type 1 diabetes
Underlying pathophysiology is insulin resistance
*risk is correlated with:
age
obesity
family hx
Type 2 diabetes
Elevated blood sugar causes serum hyper-osmalarity, which can cause:
- polydypsia
- polyuria
Extreme hyperglycemia can cause massive fluid shifts. This can result in massive osmotic diuresis (renal water loss) and subsequent hypotension
*can lead to coma
Hyperosmolar nonketotic state
more likely in type 2
Fasting plasma glucose >126
Random glucose >200 with polyuria and polydipsia
2 hours post glucose tolernce test plasma glucose >200
Diabetes diagnosis
Common diabetic drug treatment that decreases hepatic gluconeogenesis
Metformin
Sulfonylureas increase….
insulin secretion
Thiazolinediones decrease…
insulin resistance
Glucagon
Epinepherine/Norepinepherine
Glucocorticoids
Growth hormone
..all do what to blood sugar levels?
INCREASE
Anxiousness
Diaphoresis
Tachycardia
…signs of?
HYPOglycemia
________ is defined by Whipple’s triad
Hypoglycemia
Low plasma glucose
Symptoms of hypoglycemia
Response to carbohydrates
Whipple’s triad
seen in hypoglycemia
What do PTH and vitamin D do to calcium levels?
What about calcitonin?
PTH and Vit D increase calcium levels
Calcitonin decrease calcium levels
Stimulate osteoclasts to break down bone
increase reabsorption of calcium by kidneys
increase conversion of inactive vitamin D to active vitamin D
ways PTH increases calcium
Vitamin D increases absorption of _______ and ______ from gut
calcium and phosphate