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200 Cards in this Set
- Front
- Back
Describe Negative Feedback loops
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1. Control an increase or decrease in hormone production
2. Examples: Increased Ca decreased PTH, Decreased Ca increases PTH |
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What is the purpose of stimulation tests?
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Evaluate for hypofunctioning disorders
-Example: Adrenocorticotropic hormone (ACTH) stimulation test is used in the workup of hypocortisolism |
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What are the causes of endocrine hypofunction?
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1. Autoimmune destruction
-Examples: Addison’s disease, Hashimoto’s Thyroiditis 2. Infarction -Examples: Sheehan’s postpartum necrosis, Waterhouse-Friderichsen syndrome 3. Decreased hormone stimulation -Example: Decreased TSH in hypopituitarism 4. Enzyme deficiency, infection, neoplasia, congenital disorder |
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What is the most common cause of endocrine gland hypofunction?
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Autoimmune disease
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What is the purpose of suppression tests?
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1. Evaluate hyperfunctioning disorders
-Example: Dexamethasone suppression test evaluates hypercortisolism 2. Most hyperfunctioning disorders cannot be suppressed -Notable exceptions are prolactinoma and pituitary Cushing syndrome |
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What are the causes of endocrine hyperfunction?
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-Adenoma
-Acute inflammation -Hyperplasia -Cancer |
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What is the most common cause of endocrine gland hyperfunction?
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Benign adenoma
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What tumors alter hypothalamic function?
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1. Pituitary adenoma
-Most common tumor affecting the hypothalamus 2. Craniopharyngioma 3. Midline hamartoma -Not a neoplasm 4. Langerhans histiocytosis |
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What inflammatory disorders alter hypothalamus function?
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1. Sarcoidosis
-Produces granulomatous inflammation 2. Meningitis |
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Describe the clinical findings of hypothalamic dysfunction
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1. Secondary hypopituitarism
-No releasing hormones to stimulate the anterior pituitary 2. Central diabetes inspidus (CDI) -Antidiuretic hormone (ADH) is synthesized in the hypothalamus 3. Hyperprolactinemia -Loss of dopamine inhibition causes galactorrhea 4. Precocious puberty -Most common cause in boys in a midline hamartoma 5. Visual field disturbances -Usually bitemporal hemianopia 6. Mass effects -Produces obstructive hydrocephalus 7. Growth disorders -Dwarfism in children 8. Kallmann’s syndrome |
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Describe “True” precocious puberty in boys
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-Implies a CNS origin for the disorder, but pseudo-precocious puberty implies a peripheral cause (adrenogenital syndrome)
-True precocious puberty in boys is the onset of puberty before 9 year of age -Most common cause is a midline hamartoma in the hypothalamus |
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Describe “True” precocious puberty in girls
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-Implies a CNS origin for the disorder, but pseudo-precocious puberty implies a peripheral cause (adrenogenital syndrome)
-True precocious puberty in girls is the onset of puberty before 8 years of age -In most cases, it is idiopathic and less likely to be caused by a midline hamartoma |
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Describe the clinical anatomy of the pineal gland
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1. Midline location above the quadrigeminal plate
2. Site for melatonin production a. Superior cervical sympathetic ganglia stimulates receptors on pinealocytes -Causes release o melatonin into spinal fluid and blood b. Melatonin functions i. Important in sleep/moods and circadian rhythms -Released at night ii. Used in the treatment of sleep and mood disorders |
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Describe melatonin
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The chemical messenger of darkness
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Describe pineal gland dystrophic calcification
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1. Begins in childhood
2. Useful in sowing shifts due to mass lesions in the brain 3. Approximately 80% are calcified between 70 and 80yo |
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Describe Pineal tumors
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1. Majority are germ cell tumors resembling seminomas
2. Minority of tumors are teratomas |
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Describe the clinical findings with pineal gland disorders
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1. Visual disturbances
-Paralysis of upward conjugate gaze (Parinaud’s syndrome) 2. Obstructive hydrocephalus -Due to compression of the aqueduct of Sylvius in the 3rd ventricle |
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Describe the epidemiology of anterior pituitary hypofunction
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1. Partial or complete loss of secretion of one or more hormones
-Infarctions of the pituitary invariably lead to pan hypopituitarism 2. Increased incidence of vascular or cerebrovascular disease 3. Types of pituitary dysfunction a. Primary hypopituitarism (pituitary dysfunction) -Approximately 75% of the gland must be destroyed b. Secondary hypopituitarism (hypothalamic dysfunction) -Decreased hypothalamic releasing factor |
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List the causes of hypopituitarism
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1. Nonfunctioning (null) pituitary adenoma
2. Craniopharyngioma 3. Sheehan’s postpartum necrosis 4. Pituitary apoplexy 5. Sickle cell anemia 6. Lymphocytic hypophysitis 7. Empty sella syndrome 8. Hypothalamic dysfunction |
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Describe nonfunctioning (null) pituitary adenoma
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1. Most common cause of hypopituitarism
2. Microadenoma <10mm, Macroadenoma > 10mm 3. Association with multiple endocrine neoplasia (MEN) I syndrome 4. MEN I syndrome findings include pituitary adenoma, hyperparathyroidoism, pancreatic tumor (Zollinger-Ellison syndrome or insulinoma) |
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Describe Craniopharyngioma
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1. Most common cause of hypopituitarism in children
2. Benign pituitary tumor derived from Rathke’s pouch remnants 3. Located above the sella turcica -Extends into sella turcica and destroys the gland 4. Cystic tumor with hemorrhage and calcification 5. Commonly causes bitemporal hemianopia 6. May produce central diabetes insipidus |
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Describe Rathke’s pouch
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An ectodermal derivative derived from the oral cavity. It develops into the anterior lobe of the pituitary gland
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What are the findings in MEN I syndrome?
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1. Pituitary adenoma
2. Hyperparathyroidism 3. Pancreatic tumor |
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What is the most common cause of hypopituitarism in children
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Craniopharyngioma
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Describe Sheehan’s postpartum necrosis
1. Hypovolemic shock (eg blood loss) causes infarction 2. Sudden cessation of lactation due to loss of prolactin -Eventual development of hypopituitarism |
Describe the changes to the pituitary gland in pregnancy
The pituitary gland doubles in size during pregnancy due to synthesis of prolactin. Prolactin release is inhibited by estrogen and progesterone during pregnancy |
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Describe Pituitary apoplexy
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1. Term apoplexy refers to a sudden onset of neurologic dysfunction
2. Most often due to hemorrhage/infarction of preexisting pituitary adenoma |
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Describe the predisposing factions to pituitary apoplexy
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1. Trauma
2. Pregnancy (Sheehan’s postpartum necrosis, a nontumorous cause) 3. Treatment of a prolactinoma with bromocriptine |
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Describe the clinical findings of Pituitary apoplexy
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Sudden onset of:
1. Headache, mental status dysfunction, visual disturbances 2. Hormone dysfunction |
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Describe anterior pituitary hypofunction from sickle cell anemia
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There is pituitary infarction from vascular occlusion by irreversibly sickled cells
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Describe Lymphocytic hypophysitis
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1. Female dominant autoimmune destruction of the pituitary gland
2. Occurs during or after pregnancy |
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Describe the epidemiology of Empty sella syndrome
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1. Radiologic studies show an empty sella turcica
2. Primary and secondary types |
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Describe the primary type of empty sella syndrome
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1. Anatomic defect above pituitary
2. Subarachnoid space extends into sella turcica and fills up with CSF 3. Increase in pressure on the pituitary gland causes it to flatten out 4. Often associated with women who are obese and have high BP |
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Describe the secondary type of empty sella syndrome
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Regression in size due to radiation, trauma, surgery
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Describe how to make the diagnosis of hypopituitarism
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1. CT scan or MRI (better test) of sella turcica
2. Stimulating tests for the various deficiencies |
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Describe the treatment of hypopituitarism
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1. Surgery for tumors (usually transsphenoidal)
2. Hormone replacement for deficiencies |
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What hormones are deficient in hypopituitarism
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1. Gonadotropins (FSH, LH)
2. Growth hormone (GH) 3. Thyroid-stimulating hormone (TSH) 4. Adrenocorticotropic hormone (ACTH) |
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Describe Gonadotropin deficiency in hypopituitarism
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1. Children have delayed puberty
2. Adult females have secondary amenorrhea; produces osteoporosis, hot flashes (lack of estrogen), decreased libido 3. Males have impotence, due to decreased libideo from decrease testosterone |
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Describe the GnRH stimulation test
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1. No significant increase in FSH/LH in hypopituitarism
2. Eventual increase of FSH/LH in hypothalamic disease |
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Describe the Metyrapone test
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-Stimulation test of pituitary ACTH reserve
-Metyrapone inhibits adrenal 11-hydroxylase, which casuses a decrease in cortisol and a corresponding increase in plasma ACTH (pituitary) and 11-deoxycortisol (adrenal), which is proximal to the enzyme block -In hypopituitarism, neither ACTH or 11-deoxycortisol are increased |
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Describe growth hormone deficiency in hypopituitarism
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-Decreased GH decreases synthesis and release of IGF-1
-Children have growth delay: delayed fusion of epiphyses; bone growth does not match the age of the child -Adults have hypoglycemia: decreased gluconeogenesis; loss of muscle mass; increased adipose around waist |
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Describe arginine and sleep stimulation tests
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-No increase in GH or IGF-1
-Normally, GH and IGF-1 are reelased at 5AM |
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Describe TSH deficiency in hypopituitarism
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1. Secondary hypothyroidism: decreased serum T4 and TSH
2. Cold intolerance, constipation, weakness 3. No increase in TSH after TRF stimulation |
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Describe ACTH deficiency in hypopituitarism
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1. Secondary hypocortisolism: decreased ACTH and cortisol
2. Hypoglycemia: decreased gluconeogenesis 3. Hyponatremia: mild SIADH (loss of inhibitory effect of cortisol or ADH) 4. Weakness, fatigue levels |
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Describe the Short ACTH stimulation test
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No increase in serum cortisol over decreased baseline in hypopituitarism
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Describe the Prolonged ACTH stimulation test
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Eventual increase in cortisol over the decreased baseline value once the adrenal gland is restimulated
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Describe the normal function of the posterior pituitary
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1. Stores ADH
a. Controls total body water b. Presence of ADH produces concentration of urine c. Absence of ADH produces dilution of urine 2. Releases oxytocin -Produces milk ejection and uterine contractions |
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List the pituitary hyperfunction disorders
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1. Prolactemia
2. Growth hormone adenoma 3. Syndrome of inappropriate ADH (SIADH) |
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Describe the epidemiology of prolactinoma
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1. Benign adenoma
2. Overall most common pituitary tumor (35%) 3. Secrete growth hormone as well in 7% of cases |
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Describe the clinical and laboratory findings of prolactinoma in women
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1. Seconadry amenorrhea
-Prolactin inhibits GnRH 2. Galactorrhea 3. Serum prolactin level is usually >200 mg/mL 4. Decreased FSH and LH -Due to decreased GnRH |
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Describe the clinical and laboratory findings of prolactemia in men
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1. Impotence
-Lost of libido due to decrease in testosterone 2. Headache -Tumors tend to be larger than in women 3. No enough estrogen-dependent breast tissue to produce glactorrhea 4. Serum prolactin level is usually >200 mg/mL 5. Decreased FSH and LH -Due to decreased GnRH |
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Describe the treatment of prolactinoma
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1. Dopamine analoges (eg cabergoline)
a. Tumor does respond to suppression -Shrinks in <50% of cases b. Restores gonadal function in 70% to 90% of cases 2. Surgery if macroadenomas |
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What is the most common pituitary tumor?
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Prolactinoma
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Describe the epidemiology of growth hormone adenomas
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1. Accounts for 20% of all pituitary adenomas
2. Functions of GH a. Stimulates liver synthesis/release of insulin growth factor (IGF)-1 b. Stimulates gluconeogenesis and amino acid uptake in muscle c. Negative feedback relationship with glucose and IGF-1 d. Antiatriuretic action (retains Na) 3. Functions of IGF-1 -Stimulates growth of bone (linear and lateral), cartilage, soft tissue |
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Describe the clinical and laboratory findings with growth hormone adenomas
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1. Children develop gigantism
2. Adults develop acromegaly 3. Increased GH and IGF-1 (more sensitive test than GH) 4. Hyperglycemia 5. Hypertension 6. Visceral organomegaly with dysfunction 7. Muscle weakness (myopathy); cardiomyopathy 8. Headache and visual field defects |
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Describe gigantism from growth hormone adenomas in children
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1. Gigantism due to increased linear bone growth (epiphyses have not fused)
2. Lateral bone growth is also increased |
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Describe acromegaly from growth hormone adenomas in adults
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1. Increased lateral bone growth (eg, hands, feet, jaw)
-No linear growth because epiphyses are fused 2. Prominent jaw -Spacing between teeth 3. Frontal bossing -Enlarged frontal sinus increases the hat size 4. Macroglossia, cardimyopathy (cause of death) |
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Describe the increased GH and IGF-1 in growth hormone adenomas
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Hormones not suppressed by glucose administration
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Describe the hyperglycemia in growth hormone adenomas
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Due to increase in gluconeogenesis
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Describe the hypertension in growth hormone adenomas
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Sodium retention related to increased GH and insulin (hyperglycemia increases its release)
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What organs experience visceral organomegaly with dysfunction in growth hormone adenomas
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-Heart
-Liver -Kidneys -Thyroid |
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What causes the headache and visual field defects in growth hormone adenoma?
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Enlarged sella
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How do you diagnose growth hormone adenomas?
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1. Imaging with CT scan, MRI (best study)
2. Suppression tests |
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Describe treatment of growth hormone adenomas
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1. Transphenoidal surgery
2. If surgyer does not correct: -Somatostatin and dopamine analogues; GH receptor antagonists |
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Describe the steps in thyroid hormone synthesis
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1. Trapping of iodide is TSH mediated
2. Oxidation of iodides to iodine is peroxidase-mediated 3. Organification a. Iodine is incorporated into tyrosine to form MIT (monoiodotyrosine) and DIT (diiodotyrosine) b. It is TSH-mediated 4. Coupling of MIT with DIT produces triiodothyroinine (T3) 5. Coupling of DIT with DIT produces thyroxin (T4) 6. Hormones are stored as colloid 7. Proteolysis of colloid by lysosomal proteases is TSH-mediated 8. T4 and T3 bind to thyroid-binding globulin (TBG) -One third of TBG binding sites are normally occupied 9. Free T4 (FT4) is peripherally converted to free T3 (FT3) by an outer ring deiodinase |
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Describe Free T3
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FT3 is a metabolically active hormone
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Describe Free T4
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FT4 is considered a prohormone
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Describe the relationship between T3, T4, and TSH
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-FT4 and FT3 have a negative feedback relationship with TSH
a. An increase in FT4/FT3 should produce a decrease in TSH b. A decrease in FT4/FT3 should produce an increase in TSH |
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Describe the functions of thyroid hormone
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1. Control of total energy expenditure
2. Growth and maturation of tissue 3. Turnover of hormones and vitamins 4. Cell regeneration |
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Describe Total serum T4 tests
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1. Represents T4 bound to TBG and free T4
2. Increase in TBC synthesis increases total serum T4 3. Decrease in TBC synthesis decreases total serum T4 4. Normal TBG with increase or decrease in total serum T4 a. Increase or decrease in FT4 must be present b. Increased FT4- Graves’s disease, thyroiditis c. Decreased FT4 – hypothyroidism |
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Describe Serum TSH tests
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1. Best overall screening test for thyroid dysfunction
2. Increased TSH -Primary hypothyroidism 3. Decreased TSH a. Thyrotoxicosis (eg Graves’s disease) b. Hypopituitarism/hypothalamic dysfunction -Causes secondary/tertiary hypothyroidism, respectively |
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Describe I131 radioactive uptake tests
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1. Evaluates synthetic activity of the thyroid gland
-Iodide is used to synthesize thyroid hormone 2. Increased uptake indicated increased synthesis of T4 -Examples-Grave’s disease, toxic nodular goider 3. Decreased uptake if I131 a. Inactivity of the gland -Example: Patient taking thyroid hormone b. Inflammation of the gland -Example-acute/subacute/chronic thyroiditis 4. Evaluates functional status of thyroid nodules a. Decreased uptale in a nodule -“Cold” nodule-cyst, adenoma, cancer b.Increased uptake in nodule -“Hot” nodule- toxic nodular goiter |
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Describe thyroglobulin
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Marker for thyroid cancer
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Describe lingual thyroid
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1. Failure descent of thyroid anlage from the base of the tongue
-Usually represents all of the thyroid tissue 2. Clinical findings a. Dysphagia for solids b. Mass lesion 3. I131 scan locates the lesion -Also identified any other thyroid tissue that is present |
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Describe the treatment for lingual thyroid
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1. Suppression with thyroxine
-Lingual thyroids are usually hypofunctonal 2. Ablation with radioactive iodine 3. Surgery if obstructive |
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Describe Thyroglossal duct cysts
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1. Cystic midline mass that is close to or within the hyoid bone
2. Surgery with removal of the proximal duct and hyoid bone |
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What does a mass at the base of the tongue indicate?
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Lingual thyroid
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Describe acute thyroiditis
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1. Bacterial infection (eg S. aureus)
2. Clinical findings a. Fever b. Tender gland with painful cervical adenopathy c. Initial thyrotoxicosis from gland destruction -Increased serum T4, decreased serum TSH 3. Decreased I131 uptake |
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Describe the treatment of acute thyroiditis
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Penicillin or ampicillin
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Describe brachial cleft cysts
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Located in the anterolateral neck
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Describe subacute granulomatous thyroiditis
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1. Viral infection (eg coxsackievirus, mumps)
2. Occurs most often in women 40-50yo 3. Granulomatous inflammation with multinucleated giant cells 4. Decreased I131 uptake |
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Describe the clinical findings of subacute granulomatos thyroiditis
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1. Most common cause of a painful thyroid gland
2. Often preceded by an upper respiratory infection 3. Cervical adenopathy is not prominent 4. Initial thyrotoxicosis from gland destruction -Increased serum T4, decreased TSH 5. Permanent hypothyroidism is uncommon |
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Describe the treatment of subacute granulomatous thyroiditis
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Self-limited; does not require treatment
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What is the most common cause of a painful thyroid gland?
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Subacute granumomatous thyroiditis
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Describe the epidemiology of Hashimoto’s thyroiditis
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1. Autoimmune thyroiditis
2. Incidence increases with age 3. More common in women than men 4. Human leukocyte antigen (HLA)-Dr3 and –Dr5 associations 5. Increased indecence in: -Turner’s syndrome, Down syndrome, Klinefelter’s syndrome 6. Increased incidence of other autoimmune diseases (eg, pernicious anemia) |
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Describe the pathogenesis of Hashimoto’s thyroiditis
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1. Cytotoxic T cells destroy parenchyma (type IV hypersensitivity)
-Initial thyrotoxicosis, eventual hypothyroidism 2. Blocking IgG autoantibodies against the TSH receptor -Decrease hormone synthesis; type II hypersensitivity 3. Antimicrosomal and thyroglobulin antibodies -Develop as a result of gland injury; no causal role |
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Describe the gross and microscopic findings in Hashimoto’s thyroiditis
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1. Enlarged, gray gland
2. Lymphocytic infiltrate with prominent germinal follicles |
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Describe the clinical findings in Hashimoto’s thyroiditis
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1. Most common cause of primary hypothyroidism
2. Initial thyrotoxicosis from gland destruction -Known as hashitoxicosis 3. Signs of hypothyroidism 4. Risk factor for primary B-cell malignant lymphoma of the thyroid |
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Describe Hashimoto’s thyroiditis
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1. Autoimmune thyroiditis
2. Type IV (mainly) and type II hypersensitivity 3. Most common cause of hypothyroidism |
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What is the most common cause of hypothyroidism?
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Hashimoto’s thyroiditis
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Describe Reidel’s thyroiditis
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1. Fibrous tissue replacement of the gland
2. Extension of fibrosis into surrounding tissue -Can produce tracheal obstruction 3. Associated with other sclerosing conditions -Exmaple: sclerosing mediastinitis 4. Hypothyroidism may occur |
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Describe the treatment for Reidel’s thyroiditis
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1. Initial treatment with corticosteroids
2. Tamoxifen -First-line therapy or if corticosteroids are unsuccessful 3. Surgery |
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Describe Subacute painless lymphocytic thyroiditis
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1. Autoimmune disease that develops post partum
2. Gland lacks germinal follicles |
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Describe the clinical findings in subacute painless lymphocytic thyroiditis
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1. Abrupt onset of thyrotoxicosis due to gland destruction
2. Gland is slightly enlarged and painless 3. Progresses to primary hypothyroidism in 40% to 50% of cases 4. Antimicrosomal antibodies (50%-80%) |
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Describe the treatment for subacute painless lymphocytic thyroiditis
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Levothyroxine in the hypothyroid stage
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Describe hypothyroidism
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-Reduced secretion of thyroid hormone
a. Patients are hypometabolic b. Decrease in the basal metabolic rate |
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Describe the causes of hypothyroidism
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1. Hashimoto’s thyroiditis
2. Subacute painless lymphocytuc thyroiditis 3. Hypopituitarism, iodine deficiency, enzyme deficiency 4. Drugs -Amiodarone, lithium, sulfonamides, phenylbutazone 5. Hypothalamic dysfunction/hypopituitarism 6. Congenital |
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Describe Cretinism
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1. Hypothyroidism in infancy or early childhood
2. Brain requires thyroxine for its maturation 3. Causes a. Maternal hypothyroidism -Before the fetal thyroid is developed b. Enzyme or iodine deficiency |
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Describe the clinical findings of cretinism
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1. Severe mental retardation
2. Increased weight and short stature -Pituitary dwarfism- decreased weight and short stature |
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Describe the treatment for hypothyroidism
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Thyroid hormone replacement
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What organ requires thyroxine for maturation?
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Brain
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What is the most common cause of cretinism?
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Maternal hypothyroidism before fetal thyroid development
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What are the clinical findings with adult hyperthyroidism?
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1. Proximal muscle myopathy
2. Weight gain 3. Dry and bridle hair; loss of outer 1/3 of eyebrow 4. Bradycardia 5. Coarse yellow skin 6. Perioribtal puffiness, hoarse voice 7. Fatigue, cold intolerance, constipation 8. Menstrual irregularities 9. Diastolic hypertension 10. Congestive (dilated) cardiomyopathy with biventricular heart failure 11. Atherosclerotic coronary artery disease 12. Delayed recovery of Achilles reflex, mental slowness, dementia |
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Describe the proximal muscle myopathy in adult hypothyroidism
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1. Very common finding
2. Increased serum creatine kinase |
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Describe the weight gain in adult hypothyroidism
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Due to hypometabolic state with retention of water and salt
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Describe the coarse yellow skin in adult hypothyroidism
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Yellow skin due to less conversion of beta-carotenes into retinoic acid
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Describe the periorbital puffiness and hoarse voice in adult hypothyroidism
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1. Both of these are due to myxedema
2. Increased hyaluronic acid and chondroitin sulfate in interstitial tissue 3. Nonpitting edema |
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Describe the menstrual irregularities in adult hypothyroidism
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Most often menorrhagia
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Describe the diastolic hypertension in adult hypothyroidism
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Due to retention of Na and water
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Describe the laboratory findings in hypothyroidism
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1. Decreased serum T4, increased serum TSH
2. Antimicrosomal, antiperoxidase, and antithyroglobulin antibodies -Present in Hashimoto’s thyroiditis 3. Hypercholesterolemia -Due to decreased synthesis of LDL receptors |
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Describe treatment of hypothyroidism
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1. Levothyroxine in small increments every 6-8 weeks
2. Bring serum TSH into normal range (euthyroid state) |
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Describe the causes of Myxedema coma
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1. Idiopathic; cold exposure
2. Use of sedatives/opiates 3. Acute illness |
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Describe the clinical findings in Myxedema coma
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1. Progressive stupor
2. Hypothermia 3. Bradycardia, hypoventilation 4. Hypoglycemia, hypocorticolism, SIADH |
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Describe the treatment of hypothyroidism
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1. Ventilatory support
2. Treat hypothermia 3. IV levothyroxine 4. High doses of corticosteroids |
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What is the mortality rate of hypothyroidism?
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20-50%
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Describe classification of thyroid hormone excess
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1. Thyrotoxicosis
-Describes hormone excess regardless of cause 2. Hyperthyroidism a. Describes hormone excess due to increased synthesis b. Examples: Graves’ disease, toxic nodular goiter |
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Describe the metabolic rate of thyroid hormone excess
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Patients are hypermetabolic
-Increase in the basal metabolic rate |
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Describe the epidemiology of thyroid hormone excess
|
1. Most common cause of hyperthyroidism and thyrotoxicosis
2. Female dominant autoimmune disease 3. HLA-B8 and HLA-Dr3 association |
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Describe the pathogenesis of thyroid hormone excess
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1. T cells induce specific B cells to produce IgG antibodies against the TSH receptor
a. Stimulating type of antibody as opposed to a blocking antibody b. Type II hypersensitivity reaction 2. Antimicrosomal and thyroglobulin antibodies are present 3. Inciting events that may initiate onset of the disease -Infection, withdrawal of steroids, iodide excess, post partum |
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Describe the thyromegaly in Graves’ disease
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1. Symmetrical, nontender
2. Scant colloid 3. Papillary infolding of the glands |
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What is the most common cause of hyperthyroidism and thyrotoxicosis?
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Graves’ disease
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Describe the clinical features unique to Graves’ disease
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1. Infiltrative opthalmopathy (exophthalmos; 50%)
a. Proptosis and muscle weakness of the eye b. Due to adipose and glycosaminoglycans deposited in orbital tissue c. IgG-TSH receptor antibodies can cross placenta and produce transient hyperthyroidism in fetus 2. Pretibial myxedema (1-2%) -Due to excess glycosaminoglycans in the dermis 3. Thyroid acropachy a. Digital swelling and clubbing of fingers b. Nails separate from nail bed (lifted up_ c. Exophthalmos and pretibial myxedema usually present |
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What are the unique features of Graves’ disease?
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1. Exophthalmos
2. Pretibial myxedema 3. Thyroid acropachy |
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Describe the features of Graves’ disease in the elderly (apathetic hyperthyroidism)
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1. Cardiac abnormalities
-Atrial fibrillation, congestive heart failure 2. Muscle weakness, rigidity 3. Thyromegaly |
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Describe toxic multinodular goiter (Plummer’s disease)
|
1. One of more nodules in a multinodular goiter become TSH-independent
2. See “hot” nodules with I131 scan 3. Distinctions from Graves’ disease -Lack exophthalmos and pretibial myxedema 4. Treatment is surgery |
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Describe the constitutional signs of all causes of thyrotoxicosis
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1. Weight loss with good appetite
2. Fine tremor of the hands 3. Heat intolerance, diarrhea, anxiety 4. Menstrual irregularities -Usually oligomenorrhea 5. Lid stare -Due to increased sympathetic stimulation of eyelid muscles |
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Describe the cardiac findings of all causes of thyrotoxicosis
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1. Sinus tachycardia (>beats/min)
2. Increased risk for atrial fibrillation 3. Systolic hypertension, high-output heart failure a. Thyroid hormone increases beta-receptor synthesis in the heart b. Excess hormone increases inotropic and chronotropic effect on the heart |
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What test should you order when a patient experiences atrial fibrillation?
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TSH test to rule out hyperthyroidism
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Describe the clinical findings in all causes of thyrotoxicosis
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1. Constitutional signs
2. Cardiac findings 3. Brisk reflexes, osteoporosis (increased bone turnover) |
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Describe the laboratory findings in all causes of thyrotoxicosis
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1. Increased serum T4, decreased serum TSH
2. Increased I131 uptake -Graves’ disease and toxic multinodular goiter 3. Decreased I131 uptake -Thyroiditis, patient taking excess thyroid hormone 4. Hyperglycemia -Increased glycogenolysis 5. Hypocholesterolemia -Increased LDL receptor synthesis 6. Hypercalcemia -Increased bone turnover 7. Absolute lymphocytosis |
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Describe the treatment for Graves’ disease
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1. Beta-blockers decrease adrenergic effects
2. Thionamides decrease hormone synthesis 3. Ablative I131 therapy in 1 year if above regimen does not work |
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Describe the causes of thyroid storm
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1. Inadequately treated patients with Graves’ disease undergo surgery
2. Infection, trauma 3. Iodine, pregnancy |
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Describe the clinical findings of thyroid storm
|
1. Tachyarrhythmias
2. Hyperpyrexia 3. Shock -Volume depletion from vomiting 4. Coma |
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Describe the treatment of thyroid storm
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1. Inhibit hormone synthesis
a. Propylthiouracil b. Iodide 2. Sympathetic blockade with beta-blockers 3. Hydrocortisone 4. Cooling blanket |
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Describe the epidemiology of euthyroid sick syndrome (ESS)
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1. Abnormalities in serum T3 and T4 but gland function appears normal
2. Associated with: -Malignancy, heart failure, chronic renal failure, sepsis, MI 3. Laboratory test alterations usually return to normal with resolution of the illness |
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Describe the pathogenesis of euthyroid sick syndrome
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1. Normally, a peripheral tissue outer ring deiodinase converts T4 into metabolically active T3
2. In ESS, outer ring deiodinase is blocked and inner ring deiodinase converts T4 into inactive reverse T3 -There are also abnormalities in thyroid-binding globulin |
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Describe the findings in the most common variant of Euthyroid sick syndrome
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1. Normal/decreased serum T4
2. Decreased serum T3 3. Normal/decreased serum TSH 4. Increased serum reverse T3 |
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Describe the treatment for euthyroid sick syndrome
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Varies from no treatment to levothyroxine during the time of the illness
|
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Describe the Serum T4, Free T4, Serum TSH, and I131 Uptake in Graves’ disease
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Serum T4: Increased
Free T4: Increased Serum TSH: Decreased I131 Uptake: Increased |
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Describe the Serum T4, Free T4, Serum TSH, and I131 Uptake in Patient taking excess hormone
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Serum T4: Increased
Free T4: Increased Serum TSH: Decreased I131 Uptake: Decreased |
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Describe the Serum T4, Free T4, Serum TSH, and I131 Uptake in Initial phase of thyroiditis
|
Serum T4: Increased
Free T4: Increased Serum TSH: Decreased I131 Uptake: Decreased |
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Describe the Serum T4, Free T4, Serum TSH, and I131 Uptake in primary hypothyroidism
|
Serum T4: Decreased
Free T4: Decreased Serum TSH: Increased I131 Uptake: Not indicated |
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Describe the Serum T4, Free T4, Serum TSH, and I131 Uptake in secondary hypothyroidism (hypopituitarism)
|
Serum T4: Decreased
Free T4: Decreased Serum TSH: Decreased I131 Uptake: Not indicated |
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Describe the Serum T4, Free T4, Serum TSH, and I131 Uptake in increased TBG (eg, excess estrogen)
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Serum T4: Increased
Free T4: Normal Serum TSH: Normal I131 Uptake: Not indicated |
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Describe the Serum T4, Free T4, Serum TSH, and I131 Uptake in decreased TBG (eg, anabolic steroids)
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Serum T4: Decreased
Free T4: Normal Serum TSH: Normal I131 Uptake: Not indicated |
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Describe nontoxic goiters
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Thyroid enlargement from excess colloid
|
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Describe the different types of nontoxic goiters
|
1. Endemic type
-Due to iodide deficiency (most common) 2. Sporadic type; causes include -Goitrogens (eg cabbage) -Enzyme deficiency -Puberty -Pregnancy |
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What is the most common type of nontoxic goiter?
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Endemic type due to iodide deficiency
|
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Describe the pathogenesis of nontoxic goiters
|
1. Absolute or relative deficiency of thyroid hormone
2. Hyperplasia/hypertrophy -Attempt to increase hormone synthesis 3. Hyperplasia/hypertrophy is followed by gland involution -Failure of gland to sustain synthesis 4. Initial diffuse thyromegaly is followed by multinodular goiter |
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Describe complications of nontoxic goiters
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1. Hemorrhage into cyst
-Produces sudden, painful, gland enlargement 2. Compression of jugular vein causing neck congestion -Called Pembertons’s sign 3. Primary hypothyroidism 4. Toxin nodular goiter -One or more nodules become TSH-independent; “hot” nodules 5. Hoarseness (compresses laryngeal nerve) 6. Dyspnea (compresses trachea) |
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Describe the treatment of nontoxic goiters
|
1. Levothyroxine reduces gland size and achieves the euthyroid state
2. Surgery if compressive symptoms persist |
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Describe the epidemiology of a solitary thyroid nodule
|
Majority are cold nodules (95%)
|
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List the causes of solitary thyroid nodules in adult women
|
1. Majority are cysts in a goiter (60%) or a follicular adenoma (25%)
2. Approximately 15% are malignant 3. Approximately 85-90% of solitary nodules are euthyroid |
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List the causes of solitary thyroid nodules in adult men and children
|
1. Majority are cysts in a goiter (60%) or a follicular adenoma (25%)
2. >15% are malignant (Greater change of malignancy than in females) 3. Approximately 85-90% of solitary nodules are euthyroid |
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How does a prior history of radiation to the head and neck change the epidemiology of solitary thyroid nodules?
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They are more likely to be malignant (40% of cases)
|
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Describe how to diagnose a solitary thyroid nodule
|
1. Fine needle aspiration (FNA) most important initial step
2. Thyroid hormone studies |
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Describe the treatment of solitary thyroid nodules
|
1. Depends on the FNA result
2. If malignant, surgical removal 3. If benign and asymptomatic, periodic follow-up |
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Describe Follicular adenomas
|
1. Most common benign tumor
-Surrounded by a complete capsule 2. Presents as a solitary “cold” nodule 3. Approximately 10% progress into a follicular carcinoma |
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What is the most common benign thyroid tumor?
|
Follicular adenoma
|
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Describe the epidemiology of papillary adenocarcinoma
|
1. Most common endocrine cancer
2. Papillary adenocarcinoma is the most common thyroid cancer (>75%) 3. Most common in women than men (3:1) -Usually occur in 2nd and 3rd decade 4. Associated with radiation exposure |
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What is the most common thyroid cancer?
|
Papillary adenocarcinoma (>75%)
|
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What is the most common endocrine cancer?
|
Papillary adenocarcinoma
|
|
Describe the gross and microscopic findings of papillary adenocarcinoma
|
1. Usually multifocal
2. Papillary fronds intermixed with follicles 3. Psammoma bodies (35-45% of cases) -Dystrophically calcified cancer cells 4. Empty-appearing nuclei -Called Orphan Annie nuclei 5. Lymphatic invasion |
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Where do papillary adenocarcinomas metastasize to?
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Cervical nodes, Lung
|
|
How do you diagnose papillary adenocarcinoma?
|
FNA
|
|
Describe the treatment for papillary adenocarcinoma
|
1. Usually subtotal or near total thyroidectomy with sampling of cervical nodes
2. Followed in a few weeks by radiotherapy with I131 3. Suppressive therapy with thyroid hormone -Tumor is TSH dependent |
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What is the 5yr survival rate for papillary adenocarcinoma?
|
>95%
|
|
Describe the epidemiology of follicular carcinomas
|
1. Most common thyroid cancer presenting as a solitary cold tumor
2. Female dominant cancer |
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What is the most common thyroid cancer presenting as a solitary cold nodule?
|
Follicular carcinoma
|
|
Describe the gross and microscopic findings of follicular carcinoma
|
1. Encapsulated or invasive
2. Neoplastic follicle invade blood vessels 3. Lymph node metastasis is uncommon |
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Where do follicular carcinomas metastasize to?
|
Bone and lung
|
|
Describe the treatment for follicular carcinoma
|
1. Usually subtotal or near total thyroidectomy with sampling of cervical nodes
2. Followed in a few weeks by radiotherapy with I131 3. Suppressive therapy with thyroid hormone -Tumor is TSH dependent |
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How do follicular carcinomas spread?
|
Hematogenously
|
|
Describe the familial type of medullary carcinoma
|
1. Associated with autosomal dominant MEN IIa/IIb
2. MEN IIa syndrome -Medullary carcinoma, hyperparathyroidism (HPTH), pheochromocytoma 2. MEN IIb (III) syndrome -Medullary carcinoma, muscosal neuromas (lip/tongue), pheochromocytoma |
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Contrast the prognosis of familial vs sporadic medullary carcinoma
|
Familial type has a better prognosis than sporadic type
|
|
What ectopic hormone is associated with medullary carcinoma?
|
ACTH, which can produce Cushing syndrome
|
|
Describe the pathogenesis of Medullary carcinoma
|
1. Tumors derive from parafollicular C cells
2. C cells synthesize calcitonin a. Tumor marker b. May produce hypocalcemia c. Converted into amyloid 3. C-cell hyperplasia is a precursor lesion -Calcitonin levels increase with infusion of pentagastrin |
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How do you diagnose Medullary carcinoma?
|
1. FNA
2. Serum calcitonin |
|
Describe the treatment of medullary carcinoma
|
1. Total thyroidectomy
2. Genetic screening for familial cases a. Detection of mutation of RET proto-oncogene b. Thyroidectomy is performed if patient is a gene carrier |
|
Describe primary B-cell malignant lymphoma
|
Most often develop for Hashimoto’s thyroiditis
|
|
Describe the epidemiology of anaplastic thyroid cancer
|
Most often occurs in elderly women
|
|
Describe the risk factors for anaplastic thyroid cancer
|
Multinodular goiter, history of follicular cancer
|
|
Describe the progression of anaplastic thyroid cancer
|
Rapidly aggressive and uniformly fatal
|
|
Describe the treatment of Anaplastic thyroid cancer
|
1. Palliative surgery; often compresses trachea
2. Irradiation or chemotherapy |
|
What is the 5yr survival rate of Anaplasic thyroid cancer?
|
<5%
|
|
Describe the origin of the superior and inferior parathyroid glands
|
They derive from the 4th pharyngeal pouch and the 3rd pharyngeal pouch respectively
|
|
Describe the actions of PTH
|
1. Increases Ca reabsorption in the early distal tubule
2. Decreases bicarbonate reclamation in the proximal tubule 3. Decreases phosphorus reabsorption in the proximal tubule 4. Maintains ionized Ca level in blood -Increases bone resorption and renal reabsorption of Ca 5. Increases synthesis of 1-α-hydroxylase in the proximal renal tubule a. Increases synthesis of 1,25 (OH)2D (dihydroxycholecalciferol; calcitriol) b. Inhibits 24-hydroxylase in proximal tubule, which normally converts 25-hydroxycholecalciferol synthesized in hte liver to inactive 24,25-(OH2)D 6. Stimulated by hypocalcemia and hyperphosphatemia 7. Suppressed by hypercalcemia and hypophosphatemia |
|
Describe Vitamin D intake
|
Preformed vitamin D in the diet consists of cholcalciferol (fist) and ergocalciferol (plants)
|
|
Describe endogenous synthesis of vitamin D
|
Endogenous synthesis of vitamin D in the skin occurs by photoconversion of 7-dehydrocholesterol via sunlight to vitamin D3 (cholecalciferol)
|
|
Where does reabsorption of vitamin D occur?
|
Small intestine
|
|
Describe what occurs to vitamin D after it enters the body
|
1. Liver hydroxylation of precursor vitamin D to 25-hydroxyvitamin D (25-(OH)D; calcidiol)
-Occurs in the cytochrome P450 system 2. 25-(OH)D is secreted into the blood and bound to a protein for delivery to the proximal tubules of the kidneys 3. Kidney hydroxylation of 25-(OH)D by 1α-hydroxylase produces 1,25-(OH)2-D (Active form of vitamin D; calcitriol) -If PTH is decreased, 1α-hydroxylase is decreased, and 24-hydroxylase in the proximal tubule converts 25-(OH)D to metabolically inactive 24,25-(OH)2D 4. Calcitriol attaches to nuclear receptors in target tissues |
|
Describe the functions of calcitriol
|
1. Increased Ca reabsorption in duodenum
2, Increased phosphorus reabsorption in jejunum and ileum 3. Increases bone resorption -Induces monocytic stem cells to become osteoclasts |
|
Describe the feedback control of calcitriol
|
1, Decreased serum calcium: Increased PTH > Increased synthesis of 1α-hydroxylase > Increased synthesis 1,2-(OH)2-D and via inhibition of 24-hydroxylase > Decreased synthesis of metabolically inactive 24,25-(OH)2D
2. Increased serum Ca: Decreased PTH > Decreased synthesis of 1α-hydroxylase > Decreased synthesis 1,24-(OH)2_D and via activation of 24-hydroxylase > Increased synthesis of metabolically inactive 24,25-(OH)2D |
|
What is the major source of vitamin D?
|
Sunlight
|
|
Describe the components of total serum calcium
|
1. Calcium bound to albumin (40%) and phosphorus and citrate (13%)
a. Albumin has the most acidic amino acids b. At a normal pH of 7.4, ~40% of the acidic groups are COO- and can bind to positively charged Ca 2. Free, ionized Ca (47%) -Metabolically active fraction has a negative feedback with PTH |
|
Describe hypoalbuminemia
|
1. Decreased total serum calcium
-Due to a decrease in calcium bound to albumin 2. Normal free ionized level, normal PTH 3. No evidence of tetany |
|
Describe the effect of respiratory or metabolic alkalosis on total serum Ca
|
1. Increases negative charges on albumin
2. Total serum calcium remains normal 3. Decreased ionized Ca, increased PTH 4. Patient develops tetany |
|
Describe the increase in negative charges on albumin in respiratory/metabolic alkalosis and its effect on total serum Ca
|
1. Due to fewer hydrogen ions on the COOH groups of acidic amino acids
-Change of COOH groups to COO- -Extra negative charges bind some of the ionized Ca |
|
Describe why tetany occurs in respiratory/metabolic acidosis
|
1. Although serum PTH is in equilibrium with ionized Ca, it cannot keep pace with the binding of ionized Ca to the negative charges on albumin and hence, tetany occurs
|
|
Describe tetany
|
-Due to a decreased ionized calcium level
-Causes partial depolarization of nerves and muscle a. Lowers the threshold potential (Et) -Comes closer to the resting membrane potential (Em) b. A smaller stimulus is required to initiate an action potential |
|
Describe the clinical findings of tetany
|
1. Carpopedal spasm
-Thumb flexes into the palsm 2. Chvostek's sign -Facial twitch after tapping the facial nerve |