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357 Cards in this Set
- Front
- Back
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describe the development of the thyroid gland
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develops from an evagination of the developing pharyngeal epithelium that descends from the foramen cecum, then descends to its normal position in the neck
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what is the normal weight of a thyroid?
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15-25g
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where and how is T4 -> T3?
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in the periphery
(deiodinated) |
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four cellular effects of thyroid hormone?
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1. upregulation of CHO and lipid metabolism
2. increased protein synthesis 3. increase basal metabolic rate 4. critical in brain development |
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thyroid changes during stress or pregnancy?
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increases in size, becomes more active
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function of parafollicular cells in the thyroid?
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secrete calcitonin
(aka. C cells) |
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function of calcitonin?
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increases Ca++ absorption, decreases bone resorption
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MCC of thyrotoxicosis?
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Grave's disease
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in relation to hyperthyroidism:
why is the skin warm and flushed? |
peripheral vasodilation
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cardiac manifestations of hyperthyroidism?
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1. increased CO
2. tachycardia, palpitations, cardiomegaly 3. CHF (hyperthyroidism can present as MI) |
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neuromuscular manifestations of hyperthyroidism?
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1. overactivity of SNS
2. proximal muscle weakness |
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ocular changes seen in hyperthyroidism?
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lid lag with wide staring gaze (sympathetic overstimulation of levator palpebrae superioris)
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musculoskeletal manifestations of hyperthyroidism?
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1. atrophy of skeletal muscles
2. increased bone resorption (osteoporosis) |
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what is the clinical triad seen in Graves disease?
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1. hyperthyroidism
2. opthalmopathy 3. pretibial myxedema |
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which HLAs is Grave's disease associated with?
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HLA-B8 and DR3
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peak age of incidence of Graves disease?
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20-40yrs
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pathogenesis of Graves disease?
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autoimmune
thyroid stimulating IgG(TSI) binds to the TSH receptor. this stimulated adenylyl cyclase causing increased release of thyroid hormone |
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gross morphology of Graves disease?
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* symmetrically enlarged thyroid (80g or larger)
* intact capsule * cut surface is "soft and meaty" |
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microscopic characteristics of Graves disease?
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* papillae
* pale colloid, scalloped margins * lymphoid infiltrates in surrounding interstitium |
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explanation behind opthalmopathy seen in Graves?
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*mononuclear infiltrate of retro-orbital tissue
*edema of extraocular muscles *accumulation of ECM and GAGs, fatty infiltration |
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describe pretibial myxedema
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scaly induration and thickening of skin
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what is the most common cause of hypothyroidism in iodine-sufficient areas?
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Hashimotos thyroiditis
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besides Hashimotos: other causes of primary hypothyroidism?
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1. iodine deficiency
2. surgical/radiation induced 3. drugs 4. congenital defect |
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cause of secondary hypothyroidism?
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deficient production of TSH by the pituitary
(could be due to pituitary tumor, postpartum necrosis, trauma) |
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cause of tertiary hypothyroidism?
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RARE, due to hypothalamic failure
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what is Cretinism?
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hypothyroidism develping in infancy or early childhood
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which thyroid related hormones cross the placenta and are critical to fetal brain development?
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T3 and T4
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where is cretinism most commonly seen?
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in areas where iodine deficiency is endemic
(inborn errors of metabolism occur but are rare) |
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clinical features of cretinism? (4)
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1. severe mental retardation
2. short stature 3. coarse facial features with protruding tongue 4. umbilical hernia |
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pathogenesis of myxedema?
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accumulation of ECM (GAGs) in the skin, subcutaneous tissue and viscera
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clinical features of hypothyroidism?
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*generalized fatigue, apathy
*mental sluggishness *cold-intolerant *overweight *reduced cardiac output *decreased SNS activity *cool, pale skin *myxedema |
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Hashimotos is linked to which HLA types?
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HLA-DR5, DR3
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peak age of onset of Hashimotos?
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45-65 yrs
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pathogenesis of Hashimotos?
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initiating event: sensitization of autoreactive CD4 helper T cells to thyroid antigen.
*get CD8 mediated (cytotoxic) death *also get cytokine mediated death |
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gross characteristics of hashimotos thyroiditis?
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diffusely enlarged
capsule intact cut surface is firm yellow/tan |
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microscopic characteristics of Hashimotos thyroiditis?
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*Germinal centers
*extensive inflammatory infiltrate *Hurthle cell change *fibrosis |
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clinical presentation of Hashimotos?
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painless enlarged thyroid
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hashimotos thyroiditis increases the risk of developing? (2)
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1. other autoimmune diseases
2. B-cell non-Hodgkins lymphoma |
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which thyroiditis is thought to be caused by a viral infection and is self-limited?
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Subacute granulomatous thyroiditis ("De Quervain" thyroiditis)
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which sex is Subacute granulomatous thyroiditis ("De Quervain" thyroiditis)MC seen in?
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females
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what is the peak age of onset of Subacute granulomatous thyroiditis ("De Quervain" thyroiditis)?
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30-50 yrs
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gross morphology of a thyroid with Subacute granulomatous thyroiditis ("De Quervain" thyroiditis)?
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enlarged firm thyroid
intact capsule |
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histological characteristics of Subacute granulomatous thyroiditis ("De Quervain" thyroiditis)?
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*multinucleated giant cells
*chronic inflammatory cells *damaged thyroid follicles |
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clinical presentation/course of Subacute granulomatous thyroiditis ("De Quervain" thyroiditis)?
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* presents with fever, fatigue, neck pain
* inflammation and resultant hyperthyroidism are transient (2-6) wks * may be followed by a period of hypothyroidism * full recovery within 6-8 wks |
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which thyroiditis is known as the painless or silent thyroiditis?
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subacute lymphocytic thyroiditis
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clinical s/s of subacute lymphocytic thyroiditis?
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*mild hyperthyroidism, gland enlargement
*lasts 2-8 wks *see postpartum |
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pathogenesis of subacute lymphocytic thyroiditis?
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unknown
(thought to be AI) |
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histological characteristics of subacute lymphocytic thyroiditis?
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*lymphocytic infiltrate
*hyperplastic germinal centers *patchy disruption fo thyroid follicles |
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which rare thyroid disorder mimics malignant cancer?
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Riedel thyroiditis
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micro characteristics of Riedel thyroiditis?
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extensive fibrosis of thyroid and contiguous neck structures
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etiology of Riedels thyroiditis?
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unknown
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Riedels thyroiditis is associated with?
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idiopathic fibrosis of other sites in the body (ie. peritoneum)
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two types of goiters?
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diffuse (simple) and multinodular
(diffuse have been known to progress to multinodular) |
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which goiter is known as a "colloid" goiter?
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diffuse (simple) goiter
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when would a diffuse goiter be seen?
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1. endemic in low iodine areas
2. sporadic (common in young females, no specific cause apparent) |
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what are the two phases of a diffuse goiter?
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1. hyperplastic phase (see scalloping, papillary infoldings, large follicles of varying sizes)
2. colloid involution (see lots of colloid) |
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what is the thyroid state in the majority of patients with a diffuse (simple) goiter?
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euthyroid
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if most patients with a diffuse goiter are euthyroid, what are the clinical manifestations (if any) due to?
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mass effect
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what is the pathogenesis of a multinodular goiter?
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recurrent episodes of hyperplasia and involution
(diffuse goiter can progress to multinodular goiter) |
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gross morphology of a multinodular goiter?
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multinodular, asymmetric (2000g or greater)
* cut sections show getatinous brown colloid |
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histo characteristics of a multinodular goiter?
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* hemorrhage, fibrosis, calcification, cystic change
* areas of follicular hyperplasia and inactive epithelium |
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clinical manifestations of a multinodular goiter?
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*most patients are euthyroid - therefore mass effects dominate (airway obstruction, dysphagia, large vessel compression)
* occasionally develop hyperfunctioning nodule = hyperthyroidism |
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in regards to thyroid nodules: what is the character of most solitary nodules?
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benign
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most thyroid neoplasms are of what type?
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benign adenomas (90% of the time)
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are thyroid carcinomas common?
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NO
(when they do arise, most are indolent) |
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what factors increase the risk of a thyroid nodule being neoplastic?
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*solitary
*younger patient *male patient *cold nodule *radiation history |
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are most thyroid adenomas functional or nonfunctional?
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nonfunctional
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MC type of thyroid adenoma?
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follicular adenoma (remember, benign)
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how does a follicular thyroid adenoma present?
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*unilateral painless mass
*cold nodule |
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what is needed for the definitive diagnosis of a follicular adenoma?
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histologic examination of a surgically resected specimen. Must be SURE it is not malignant.
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what three questions did Dr. Brown tell us to ask when looking at the pathologic micro slide of a nodule?
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1. encapsulated or not?
2. tissue look different? 3. compression of surrounding tissue? *if yes to all three, then its most likely a follicular adenoma |
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gross characteristics of a follicular adenoma?
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well demarced, encapsulated
avg. size ~3cm bulges from cut surface compresses adjacent thyroid |
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what is the MC form of thyroid cancer?
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papillary carcinoma (75-85%)
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peak age at diagnosis of papillary carcinoma?
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20-40 yrs
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which sex is papillary carcinoma MC in?
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females
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papillary carcinoma involves which mutations?
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RET (tyrosine kinase receptor)
BRAF RAS |
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are most papillary carcinomas solitary or multifocal?
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can be either
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characteristic histology of a papillary carcinoma?
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*papillae with a FIBROVASCULAR STALK
*ground glass (orphan Annie) nuclei *intranuclear inclusions/grooves *psammoma bodies |
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how do most papillary carcinomas present?
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as an asymptomatic thyroid nodule
(occasionally present with a cervical lymph node met) |
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prognosis of papillary carcinoma?
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excellent
10 yr survival rate >95% |
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what 3 factors would make the prognosis of a papillary carcinoma less favorable?
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1. older patient (>40)
2. extrathyroidal extension 3. distant mets (other than cervical lymph nodes) |
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what is the second MC thyroid carcinoma?
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follicular carcinoma (10-20%)
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peak age of incidence of a follicular carcinoma?
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40-50 yrs
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follicular carcinoma is more common in which sex?
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females
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~50% of cases of follicular carcinoma involve a mutation in which gene?
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RAS
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gross morphology of a follicular carcinoma?
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gray to pink/tan on cut section
(may be well circumscribed or infiltrative) |
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micro morphology of a follicular carcinoma?
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VARIES --> well differentiated follicles to nests or sheets of atypical cells
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distinction of a minimally invasive cancer from a follicular adenoma requires?
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*extensive sampling of the tumor-capsule-thyroid interface
*look for capsular and vascular invasion |
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a thyroid medullary carcinoma is a neuroendocrine neoplasm that arises from which cell?
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C cells (therefore the tumor secretes calcitonin)
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besides secreting calcitonin, what else have thyroid medullary carcinomas been known to secrete? (3)
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somatostatin
serotonin VIP |
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peak age of incidence of thyroid medullary carcinoma?
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40-50 yrs
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80% of thyroid medullary carcinomas occur sporadically. Under what conditions do the rest occur?
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MEN IIa, IIb, or familial pattern
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which gene mutation is important in the pathogenesis of thyroid medullary carcinoma?
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RET
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regarding thyroid medullary carcinoma: when would 1 nodule be seen vs. multiple nodules?
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sporadic cases - 1 nodule
familial cases - multiple nodules |
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gross and micro characteristics of thyroid medullary carcinoma?
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* firm, grey/tan
* infiltrative * nests of polygonal to spindle shaped cells * see AMYLOID DEPOSITION |
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in general, which types of thyroid medullary carcinoma would be indolent and which would be aggressive?
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indolent - familial tumors not associated with MEN
aggressive - sporadic tumors and those associated with MEN IIB |
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the rarest type of thyroid carcinoma is?
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anaplastic carcinoma
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age of incidence of anaplastic carcinoma?
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65 yrs. (older population)
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what are the three histologic variants of anaplastic carcinoma?
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1. giant cell
2. spindle cell 3. small anaplastic cell |
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anaplastic tumors may arise from?
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more differentiated tumors
(20-30% have a concurrent differentiated thyroid tumor) |
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clinical features of anaplastic thyroid tumors?
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rapidly enlarging
bulky often spreads into adjacent neck, lung mets aggressive |
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prognosis of an anaplastic thyroid tumor?
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POOR - almost 100% mortality
usually death <1 yr |
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which thyroid carcinoma is associated exposure to ionizing radiation?
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papillary carcinoma
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which thyroid carcinoma is characterized by amyloid deposition?
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medullary carcinoma
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which thyroid carcinoma is characterized by a RAS mutation 50% of the time?
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follicular carcinoma
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which thyroid carcinoma still has a good prognosis even if it mets to a cervical lymph node?
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papillary carcinoma
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which thyroid carcinoma is associated with MEN IIA and IIB?
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medullary carcinoma
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which thyrpod carcinoma is difficult to differentiate from a follicular adenoma?
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follicular carcinoma
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which two cell types is the parathyroid gland made of?
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chief cells
oxyphil cells |
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relationship between Ca++ and PTH?
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*decreased Ca++ causes PTH release
*increased Ca++ inhibits further PTH release |
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describe the metabolic functions of PTH in:
1. bone 2. kidneys (Ca++) 3. kidneys (vitamin D) 4. serum phosphate levels 5. GI Ca++ absorption |
1. activates osteoclasts
2. increases Ca++ reabsorption 3. increases conversion of vit.D to its active dihydroxy form 4. decreases (increases urinary excretion) 5. increases |
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hypercalcemia is a common complication of?
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malignancy
(due to increased bone resorption) |
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pathophys. of malignancy-induced hypercalcemia?
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*osteolytic mets release cytokines which induce osteolysis
*PTHrp (PTH related protein) is released from the tumor - this mimics PTH and binds to identical receptors *this increases serum Ca++ levels |
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PTHrp often indicates what kind of cancer?
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advanced cancer with a poor prognosis
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so what is the MCC for clinically significant hypercalcemia in adults?
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malignancy!
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what is the MC parathyroid lesion?
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adenoma (75-80%)
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in which type of parathyroid lesion are all 4 glands hyperplastic?
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primary hyperplasia
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in which sex is primary hyperparathyroidism MC in?
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females
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hyperparathyroidism is associated with what genetic syndromes?
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MEN I and II
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which parathyroid lesion presents as a solitary, enlarged lesion?
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parathyroid adenoma
(only 1 gland effected: the rest of the glands are normal size) |
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a parathyroid adenoma is made up of what type of cells?
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chief cells
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histo characteristics of a parathyroid adenoma?
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chief cells with little fat
rim of compressed normal parathyroid around the edge |
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most parathyroid adenomas are located in which parathyroid gland?
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one of the inferior glands
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primary hyperplasia can be sporadic or occur with?
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MEN I or II
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in primary hyperplasia which parathyroid glands are enlarged?
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ALL 4
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what is a rare malignancy of the parathyroid?
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parathyroid carcinoma
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how is the diagnosis of parathyroid carcinoma made?
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NOT by cytologic atypia. it is made by local invasion and metastasis
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what is the MC clinical finding of parathyroid carcinoma?
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asymptomatic increase in serum Ca++ levels
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primary hyperparathyroidism has what effects on the following:
1. bone 2. kidneys 3. GI 4. CNS 5. neuromuscular 6. cardiac |
1. fracture secondary to osteoporosis or osteitis fibrosa cystica
2. nephrolithiasis 3. constipation, nausea, peptic ulcer, pancreatitis, gallstones 4. depression, lethargy, seizures 5. weakness and fatigue 6. aortic or mitral valve calcifications |
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mneumonic for remembering how primary hyperparathyroidism presents?
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bones, stones, groans, moans
*painful bones *renal stones *abdominal groans *psych. moans |
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what is the MCC of secondary hyperparathyroidism?
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renal failure
(due to phosphorus retention. increased phosphorous causes decreased Ca++ levels --> increased PTH as a result) |
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besides renal failure - what are some other causes of secondary hyperparathyroidism? (3)
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* dietary deficiency of Ca++
* steatorrhea * vitamin D deficiency |
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in comparison to primary hyperparathyroidism - what are the bone abnormalities and other changes like?
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less severe
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which is more common: hyper or hypo parathyroidism?
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hyperparathyroidism
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causes of hypoparathyroidism?
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1. surgically induced
2. congenital absence 3. idiopathic atrophy (most likely AI) 4. familial |
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congenital absence of the parathyroid glands (along with absence of the thymus) is called?
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DiGeorge syndrome
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what are some clinical manifestations of hypoparathyroidism?
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1. tetany
2. mental status changes 3. intracranial manifestations 4. ocular disease 5. cardiac conduction deficit 6. dental abnormalities |
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what are dental abnormalities seen in hypoparathyroidism?
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1. dental hypoplasia
2. failure of erruption 3. defective enamel and root formation |
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define pseudohypoparathyroidism
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resistance of organs to normal or increased PTH
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what is the difference between pseudohypoparathyroidism type 1 and 2?
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type 1: decreased cAMP response to PTH
type 2: normal cAMP, blunted response to the 2nd messenger |
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phenotype of type 1 pseudohypoparathyroidism?
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Albright hereditary osteodystrophy (round facies, short stature, short metacarpal and metatarsal bones)
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phenotype of type 2 pseudohypoparathyroidism?
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skeletal and developmental abnormalities
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location of 5'deiodinase I and II?
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I - peripheral tissues
II - hypothalamus |
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function of deiodinase?
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converts T4 --> T3
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what hormone inhibits conversion of T4 -> T3?
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somatostatin
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which is the dominant circulating form of thyroid hormone?
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T4
(lesser acting) |
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which is the dominant acting form of thyroid hormone?
|
T3
(lesser circulating form) |
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what happens to a patient if euthyroid and given exogenous TSH?
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develops a goiter
(TSH initiates growth & development factors for thyroid follicular cells) |
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Dr. Newmans 4 categories of hypothyroidism causes?
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1. autoimmune disorders
2. congenital 3. drugs 4. therapeutic result (surgery or radiation) |
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drugs that commonly cause hypothyroidism?
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amiodarone
LiCO3 |
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what is subclinical hypothyroidism?
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patient feels fine but TSh is elevated
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what cause of hypothyroidism am I:
increased T3, T4, TSH, TRF goiter clinical picture - hypothyroidism |
resistance to thyroid hormone
(see in DM type II, also see in genetic mutations) |
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thyroid changes during a systemic illness?
|
*called non-thyroidal illness syndrome)
1. increased cortisol, DA 2. cortisol blocks deiodinase (less T3, lots of rT3) 3. decr. T3 causes hypothalamus to shut down (no feedback) 4. eventual decr. in T4 (no TSH) 5. end stage: all thyroid levels decreased |
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according to Dr. Newman: undifferentiated problems require a?
|
differential diagnosis
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what type of goiter is seen in Hashimotos disease?
|
firm, smooth, bosselated, paplable isthmus
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what type of antibodies do we test for when looking for hashimotos?
|
anti-TPO
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what is hashimotos treated with?
|
T4
(levothyroxine) |
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two reasons why we administer T4 and not T3 for hashimotos?
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1. T4 goes back to hypothal. which in turn regulates TSh levels. this gives us a tool to regulated therapy (measure TSH)
2. peripheral autoregulation of T4->T3 |
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which antibodies are known to be present in Graves disease and what do they bind to?
|
TSI (thyroid stimulating immunoglobulins) - bind to TSH receptor
|
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a "significant %" of thyroid adenomas secrete?
|
T3
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give an example of ectopic T4 production
|
struma ovarii
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what thyroid levels would you see on struma ovarii?
|
increased T4, T3 (periph. conversion)
decreased TSH, TRF no goiter |
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what would the lab values be in a TSH secreting pituitary adenoma?
|
(rare)
high TSH high T3, T4 low TRF |
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what do the hands look like in thyrotoxicosis?
|
finger tremor
moist hands warm hands hyperperfused hands |
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compare the duration of action of T4 vs. T3
|
T4 - slower acting but longer duration of action
T3 - faster acting and shorter duration of action |
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what is the binding protein for thyroid hormone?
|
TBG
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DA and glucocorticoids have what effect on TSH secretion?
|
decrease secretion
|
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why is amiodarone so likely to affect thyroid function?
|
amiodarone has iodide in it.
|
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what meds and physiologic states can cause increased levels of TBG?
|
1. estrogen
2. pregnancy 3. tamoxifen 4. methadone 5. acute hepatitis 6. familial TBG excess |
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what meds and physiologic states can cause decreased levels of TBG?
|
1. anabolic steroids
2. niacin 3. glucocorticoids 4. chronic liver disease 5. acromegaly 6. familial TBG deficiency |
|
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effects of furosemide and NSAIDs on thyroid function?
|
displace thyroid hormone binding to TBG
|
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effects of the following drugs on thyroid function?
1. phenobarbital 2. rifampin 3. phenytoin 4. carbamezapine |
(anticonvulsants) increase T3 and T4 metabolism
|
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effects of estrogen on TH?
|
*causes increased synthesis and decreased clearance of TBG by liver
* total T3 and T4 are increased, but FREE T3 AND T4 REMAIN NORMAL (see the same changes in pregnancy) |
|
|
what is the antithyroid agent of choice used to treat hyperthyroidism?
|
thionamides
* methimazole (Tapazole) * propothiouracil (PTU) |
|
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MOA of both methimazole and PTU?
|
inhibit TH synthesis by acting as an alternative substrate for the iodinating intermediate.
*inhibits TPO-mediated iodination of tyrosine residues in Tg *inhibits I- incorporation into tyrosyl residues of Tg *inhibits coupling of iodotyrosil residues into T4 or T3 *eventually stored TH is depleted |
|
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are the actions of PTU and methimazole reversible?
|
yes
(reversible upon d/c of drug) |
|
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adverse effects of thionamides?
|
*rash
*agranulocytosis *arthralgia (antithyroid arthritis syndrome) *hepatotoxicity *vasculitis |
|
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of the thionamides, which one is more hepatotoxic?
|
PTU
(other agent may be cautiously used if one causes hepatitis b/c of different hepatitis mechanisms) |
|
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vasculitis is more commonly seen with which thionamide?
|
PTU
*(causes lupus like syndrome with positive ANA) |
|
|
PTU vs. Methimazole:
which has an effect on 5'-deiodinase? |
PTU
|
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PTU vs. Methimazole:
tume to euthyroidism? |
PTU - months
methimazole - weeks |
|
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PTU vs. Methimazole:
dosing schedule? |
PTU: 2-3xd
methimazole: 1-2 xd |
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which thionamide is the drug of choice for hyperthyroidism during pregnancy and lactation?
|
PTU
(less passage thru placenta & breast milk) |
|
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which medication is the drug of choice for hyperthyroidism in a pediatric patient?
|
thionamides
|
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which thionamide is known for increasing the failure rate of I131?
|
PTU
|
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goal of treatment of graves disease with thionamides?
|
want to induce remission
(usually takes 12-18 mo) |
|
|
what is 131I used for?
what is 123I used for? |
131I - ablation therapy (beta emissions)
123I - thyroid scanning (gamma emissions) |
|
|
MOA of 131I
|
rapidly taken inot thyroid and deposited in colloid of follicles. Beta emissions produce thyroiditis and fibrosis. little damage to surrounding tissue. see improvement in 4-5 wks, euthyroidism is reached within 6-18 wks.
|
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what is the goal of 131I?
|
euthyroidism
(rarely achieved without later T4 therapy) |
|
|
how is thyroid function followed after 131I treatment?
|
*follow FT4 and/or TSH every 1-2 mo
*start T4 when FT4 is low or TSH is high |
|
|
absolute contraindications for radioiodine?
|
pregnancy, breastfeeding, children
*congenital hypothyroidism may occur *delay conception for at least 4 months after tx. |
|
|
adverse effects of radioidine?
|
*hypothyroidism
*transient worsening of opthalmopathy *painful thyroiditis *thyrotoxic crisis |
|
|
what can be done to minimize the worsening opthalmopathy after administering 131I?
|
can give prednisone tapered over 3 months
|
|
|
which has more adverse effects: antithyroid drugs or 131I?
|
antithyroid drugs
|
|
|
MOA of iodides?
|
high concentrations in follicular cells decrease TH synthesis and release, also inhibit iodide active transport.
*this temporarily reduces thyroid vascularity and size |
|
|
two iodides used?
|
pottasium iodide (SSKI)
iodine (Lugol's solution) |
|
|
what occurs to make the effects of iodides temporary?
|
"escape" occurs within 1-2 wks
|
|
|
indications for iodides?
|
*acute hyperthyroid state (thyrotoxicosis)
*pre-thyroid surgery (decrease vascularity of gland) |
|
|
adverse effects of iodides?
|
rash
salivary gland swelling hypersensitivity |
|
|
mechanism behind increased sympathetic tone in hyperthyroidism?
|
T3 regulates the transcription of genes - get an increase in beta-1 receptors. (therefore increased beta-adrenergic activity associated with elevated TH)
|
|
|
treatment for increased beta-adrenergic activity due to increased TH?
|
beta blockers
(do not prevent thyrotoxicosis) |
|
|
why is Liothyronine Sodium (Cytomel) not as commonly used as levothyroxine?
|
it has an increased risk of cardiac adverse effects
|
|
|
therapy of choice for hypothyroid patients?
|
levothyroxine (T4)
|
|
|
what is the half life of levothyroxine and what is the significance of this?
|
7 days
slow onset of action (4-5 wks to reach steady state) |
|
|
how is the efficacy of levothyroxine monitored?
|
TSH levels
(small changes in T4 dose significantly change TSH levels) |
|
|
when would you give a lower dose in starting out levothyroxine therapy?
|
elderly, CVD, or risk factors for CVD
|
|
|
how soon after each dosage change of levothyroxine should you check TSH levels?
|
6-8 wks (no sooner than 4)
|
|
|
how is the efficacy of levothyroxine monitored in the case of pituitary insufficiency?
|
FT4 and FT3
|
|
|
diabetes mellitus is diagnosed when the:
1. fasting plasma glucose is? 2. 2 hr. postload PG is? |
1. >126
2. >200 |
|
|
1. what FPG value corresponds with "prediabetes"?
2. what 2 hr postload PG corresponds with prediabetes? |
1. 100-125
2. 140-199 |
|
|
a normal FPG is?
|
<100
|
|
|
some risk factors for diabetes?
|
1. increasing age
2. obesity 3. inactivity 4. race (blacks, hispanics, asians/pacific islanders, native americans) |
|
|
90-95% of diabetics are of what type?
|
type II
|
|
|
general pathophysiology of
*type I diabetes? *type II diabetes? |
type I - failure of Beta cells (insulin deficiency)
type II - insulin resistance and insulin deficiency |
|
|
describe the progression of insulin resistance to type 2 DM
|
insulin resistance -> hyperinsulinemia -> impaired post-prandial sugars (fasting sugars are normal) -> beta cell failure -> type 2 DM
|
|
|
which type of DM:
1. requires insulin for survival? 2. displays diabetic ketoacidosis? |
1. type I
2. type I |
|
|
good control of plasma glucose has been shown to reduce?
|
retinopathy
nephropathy neuropathy macrovascular events |
|
|
which diabetic medication has been shown to have a better outcome in obese individuals?
|
metformin
|
|
|
recommendations for diabetic control are a:
1. preprandial PG of? 2. postprandial PG of? 3. AiC? |
1. 90-130
2. <180 3. <7% |
|
|
name three 2nd generation sulfonylureas used to treat DM?
|
Glipizide
(Glucotrol) Glyburide (Diabeta, Micronase, Glynase) Glimepiride (Amaryl) |
|
|
name a biguanide oral antidiabetic agent
|
metformin
|
|
|
name two alpha-glucosidase inhibitors
|
acarbose (Precose)
miglitol (Glyset) |
|
|
name two meglitinides
|
nateglinide (Starlix)
repaglinide (Prandin) |
|
|
name two thiazolidinediones
|
pioglitazone (Actos)
rosiflitazone (avandia) |
|
|
1st or 2nd line therapy for initial management of type 2 DM?
|
sulfonylureas
|
|
|
MOA of sulfonylureas?
|
*stimulate insulin secretion by pancreatic B-cell
*increases serum insulin which partially overcomes peripheral insulin resistance |
|
|
2 side effects of sulfonylureas?
|
1. hypoglycemia
2. weight gain |
|
|
MOA of meglitinides?
|
(non-sulfonylurea secretagogues)
* increase insulin secretion (need functioning B cells) |
|
|
describe the dosing of meglitinides
|
dose just prior to meals, 3 times per day
|
|
|
which gives a greater control of FPG: sulfonylureas or meglitinides?
|
sulfonylureas
|
|
|
which has less side effects:
sulfonylureas or meglitinides? |
meglitinides
(less weight gain and hypoglycemia) |
|
|
compare the onset and duration of action between sulfonylureas and meglitinides.
|
meglitinides have a shorter onset and shorter duration of action
|
|
|
MOA of alpha-glucosidase inhibitors?
|
compete with glucosidases in the intestinal brush border (they normally break down dietary carbs)
|
|
|
compare the effectiveness of alpha-glucosidases to sulfonylureas, metformin, insulin
|
least effective
|
|
|
adverse effects of alpha-glucosidase inhibitors?
|
NO weight gain
*mainly GI problems |
|
|
#1 oral antidiabetic drug?
|
metformin
|
|
|
MOA of metformin (biguanide)?
|
*requires the presence of insulin*
1. decreases basal hepatic glucose output (reduces gluconeogenesis) 2. increases peripheral glucose uptake (minor action) 3. decreases appetite |
|
|
compare the efficacy of metformin to sulfonylureas
|
similar in efficacy
|
|
|
special condition (besides DM) which metformin is indicated for?
|
PCOS
(improves ovulation and metabolic parameters) |
|
|
effect of metformin on individuals with impaired glucose tolerance?
|
may prevent or delay development of type 2 DM
|
|
|
adverse effects of metformin?
|
(little risk of weight gain or hypoglycemia)
*GI *impaired B12, folate absorption (could get magaloblastic anemia) *lactic acidosis |
|
|
what are the absolute contraindications for metformin administration because of lactic acidosis risk?
|
*CHF requiring drugs
*renal dysfunction *acute or chronic metabolic acidosis *iodinated contrast |
|
|
MOA of thiazolidinediones (TZD)?
|
* major - improves insulin sensitivity and enhances glucose utilization by adipocytes and skeletal muscle.
*minor-reduction of hepatic glucose production (does not increase insulin release, requires the presence of insulin) |
|
|
TZDs are agonists of the peroxisome proliferator activated receptor-gamma (PPAR-g). significance?
|
*found in adipose tissue, skeletal muscle, liver
*increased transcription of insulin responsive genes in control of glucose transport (inproves insulin sensitivity) |
|
|
effect of TZDs on beta cell function?
|
may preserve B-cell function
|
|
|
which TZD has a risk of OC failure?
|
pioglitazone
|
|
|
adverse effects of TZD?
|
*increased LFTs (avoid in liver disease
*fluid retention (edema, avoid in CHF) |
|
|
what is an adverse effect specific to rosiglitazone?
|
new onset and worsening of diabetic macular edema
|
|
|
techniques for preventing or delaying onset of diabetes?
|
1. lifestyle intervention
2. metformin 3. acarbose 4. troglitazone (only one with known true preventative effect) 5. orlistat (all delay onset for sure) |
|
|
2 MC adverse effects of insulin therapy?
|
weight gain
hypoglycemia |
|
|
Three rapid acting prescription insulins?
|
1. lispro (Humalog)
2. aspart (Novolog) 3. glulisine (Apidra) |
|
|
two short acting insulins that are non-prescription?
|
Humalin R
Novolin R |
|
|
difference between short acting insulins that are prescription or not?
|
prescription: can dose during a meal
non-Rx: have to plan, may need a snack |
|
|
two intermediate acting insulins?
|
NPH (Novolin N)
NPH (Humulin N) |
|
|
how often must an intermediate acting insulin be administered?
|
2x daily
|
|
|
two long acting insulins?
|
glargine (Lantus)
detemir (Levemir) |
|
|
which type of insulin is the agent of choice to be administered between meals?
|
rapid acting insulin (lispro, aspart, glulisine)
|
|
|
what is the regimen of choice in the treatment of diabetes type II?
|
1. basal (long acting) insulin -ie. Lantus
2. rapid acting with each meal (humalog, novalog) |
|
|
is there any H A1C difference if the regimen of choice were switched for regular insulin or NPH?
|
NO
(just more convenient) |
|
|
how long before a meal should the following be dosed?
1. lispro? 2. regular insulin |
1. within 15 minutes of a meal
2. 30-60 min. before meal |
|
|
how often should glargine be dosed?
|
once daily at bedtime (or AM)
|
|
|
what type of diabetes medications are exenatide (Byetta) and pramlinitide (Symlin)?
|
non-insulin injectables (NEW)
|
|
|
exanitide may be prescribed along with what other diabetes meds?
|
metformin, sulfonylureas
NOT insulin |
|
|
indications for exenatide?
|
DM type2 in patients that have been unable to control their glucose by taking metformin and/or sulfonylureas
|
|
|
MOA of exanatide?
|
*stimulates insulin release only when PG is high*
1. stimulates insulin release (in the pancreatic B cell)in response to meals 2. inhibits glucagon secretion (by the pancreatic a-cell) |
|
|
actions of exanatide on the:
1. CNS 2. liver 3. stomach |
1. promotes satiety
2. reduces glucose output by inhibiting glucagon release 3. slows gastric emptying |
|
|
indications of pramlintide (Symlin)
|
Type 1 - adjunct in pts who cannot achieve glc control despite insulin
type 2 - adjunct in pts who cannot control glc levels |
|
|
effects of pramlintide?
|
improves postprandial glucose state
|
|
|
if a pt is on pramlintide, how much should the insulin be reduced by?
|
50%
|
|
|
pramlintide has a black box warning for?
|
hypoglycemia unawareness
|
|
|
what is the theory behind combination therapy in the treatment of DM type 2?
|
low doses of 2 agents acheive better PG control with < side effects than maximal doses of 1 agent.
|
|
|
if combination therapy is ineffective in PG control - what is the last resort?
|
insulin
(don't be afraid to delay it's use) |
|
|
in relation to the endocrine pancreas:
1. A (alpha) cells make? 2. B (beta) cells make? 3. D (delta) cells make? 4. F cells make? 5. enterochromaffin cells make? |
1. glucagon
2. insulin 3. somatostatin 4. pancreatic polypeptide (PP) 5. serotonin (may give rise to carcinoid tumors) |
|
|
what type of cells are most numerous in the endocrine pancreas?
|
beta cells
|
|
|
release of glucagon is stimulated by?
|
1. decreased blood glucose
2. increased amino acids 3. acetylcholine 4. stress hormones |
|
|
effects of glucagon?
|
glycogenolysis and gluconeogenesis (liver) -> increase plasma glucose
|
|
|
where in the islet of Langerhans do the alpha cells reside?
|
periphery
|
|
|
a glucagonoma is?
|
a disorder of increased glucagon production
|
|
|
what stimulates the release of insulin from beta cells?
|
1. increased blood glucose
2. diabetic medications (sulfonylureas) 3. amino acids 4. gastrin 5. secretin 6. fatty acids |
|
|
what is meant by the fact that insulin release is biphasic?
|
two stages of insulin release: synthesis, storage, release
|
|
|
effects of insulin?
|
*anabolic effects
1. enhances receptor mediated uptake of glucose and aa by cells 2. promotes glycogen, protein synthesis 3. inhibits lipolysis |
|
|
insulin is inhibited by? (4)
|
1. somatostatin
2. epinephrine 3. glucagon 4. GH |
|
|
in what situations would a decrease in beta cells be seen (causing a decrease in the action of insulin)? (5)
|
1. DM
2. chronic pancreatitis 4. hemochromatosis 5. pancreatectomy |
|
|
2 drugs that inhibit insulin secretion?
|
phenytoin
diazoxide |
|
|
three things that decrease insulin receptors?
|
1. obesity
2. corticosteroids 3. GH |
|
|
DM type I doesn't show up clinically until how much of the beta cells are destroyed?
|
80%
|
|
|
what destroys the beta cells in DM type I?
|
CD8+ T-cell lymphocytes - "insulitis"
|
|
|
three points in the pathogenesis of DM type I?
|
1. genetic susceptibility
2. AI 3. environmental insult |
|
|
which HLA types are associated with DM type I?
|
HLA-DR3, DR4
|
|
|
explain the environmental insult that is thought to play a role in the development of DM type I?
|
possible viral infection, chemical or toxin exposure may trigger the disease
|
|
|
pathophysiology of diabetic ketoacidosis
|
cells starved for nutrients when insulin levels low. proteins and lipids hydrolized to ketones -> metabolic acidosis due to ketoacidosis and dehydration.
|
|
|
therapy for DKA?
|
insulin
fluid replacement K+ replacement *close monitoring |
|
|
what type of coma are type 2 diabetics susceptible to?
|
nonketotic, hyperosmolar coma
|
|
|
two major components of DM type 2?
|
1. inadequate insulin secretion
2. peripheral insulin resistance |
|
|
what causes the amyloid deposition seen in DM type 2?
|
amylin is secreted with insulin -> results in amyloid deposition
|
|
|
measurement of glysosylated albumin will inform you about the diabetic control how far in the past?
|
~ 3 wks
(vs. A1C - 2-4 mo) |
|
|
complications in the arteries from DM type 2?
|
coronary artery disease
cerebrovascular disease peripheral vascular disease |
|
|
complications in the arterioles from DM type 2?
|
hyaline arteriolosclerosis
|
|
|
complications in the eyes from DM type 2?
|
retinopathy
cataracts glaucoma |
|
|
difference between nonproliferative and proliferative diabetic retinopathy?
|
nonproliferative - microaneurysms, hemorrhages, exudates, capillary thickening
proliferative - prolif. of new vessels, may henorrhage or cause retinal detachment |
|
|
types of neuropathy seen in DM type 2 patients?
|
1. sensory/motor (mono- or plexo-neuropathy), dysesthesias, hyperesthesias
2. autonomic (cardiac, GI bowel motility dysfx., GU-bladder erectile dysfx.) |
|
|
what is a nesidioblastosis?
|
disorder of persistent increased insulin production in the neonate (due to a focal or diffuse increase in islets)
|
|
|
what is beta cell hyperplasia?
|
transient increased insulin production. seen in infants of mothers w/poorly controlled diabetes
|
|
|
somatostatin inhibits?
|
glucagon and insulin secretion
|
|
|
what is the triad seen in a somatostatinoma (incr. somatostatin production)?
|
1. glucose intolerance
2. steatorrhea 3. gallbladder disease |
|
|
islet cell tumors are seen in?
|
MEN I
|
|
|
"triad" of MEN I?
|
Pituitary
Parathyroid Pancreas |
|
|
what is the MC functioning islet cell tumor?
|
insulinoma
|
|
|
clinical s/s of an insulinoma?
|
sweating, palpitations, anxiety, H/A, seizures, LOC. symptoms relieved by food.
|
|
|
Tx. for insulinoma?
|
surgery
diazoxide, phenytoin, somatostatin analogues |
|
|
what type of pancreatic tumor is seen in Zollinger-Ellison syndrome?
|
gastrinoma
(can be in pancreas or duodenum) |
|
|
clinical s/s of gastrinoma?
|
abdominal pain (may have peptic ulcer)
diarrhea steatorrhea |
|
|
Tx. of a gastrinoma?
|
surgery
H+ inhibitors somatostatin analogues |
|
|
what is Verner-Morison syndrome?
|
watery diarrhea, hypokalemia, achlorhydria: all due to a VIPoma
|
|
|
normal functions of VIP?
|
stimulate gastrointestinal fluid secretion, smooth muscle relaxation, vasodilation
|
|
|
Tx. for VIPoma?
|
surgery
somatostatin analogues |
|
|
clinical s/s of glucagonoma
|
glucose intolerance
weight loss migratory erythema anemia tendency for DVT |
|
|
triad seen in somatostatinoma?
|
diabetes
steatorrhea gallbladder disease |
|
|
somatostatinoma is commonly seen with which disorder?
|
neurofibromatosis type I
|
|
|
character of somatostatinoma?
|
if in pancreas: 90% malignant
if in duodenum: 50% malignant |
|
|
T/F: most nonfunctioning tumors of the endocrine pancreas are benign
|
FALSE
>50% are malignant however, do present with mass effect |
|
|
of the following tumors: which is the most malignant?
gastrinoma, VIPoma, glucagonoma, insulinoma |
glucagonoma (60-75% malignant)
|
|
|
where is PTH synthesized?
|
chief cells of the parathyroid
|
|
|
does the parathyroid gland respond more dramatically to hyper or hypo calcemia?
|
hypocalcemia
(response curve is sigmoidal: so lower levels of Ca++ trigger a more dramatic release of PTH) |
|
|
MOA of PTH on bone?
|
activates osteoblasts: osteoblasts then secrete local factors that activate osteoclasts causing bone resorption
|
|
|
local factors secreted by osteoblasts that activate asteoclasts?
|
collagenase
matalloproteinases plasminogen activator osteoclast activating factor |
|
|
effects of intermittent PTH treatment on bone?
|
increases bone formation
(via FGF-2, IGF-1) |
|
|
12-55% of dialysis patients have what type of hyperparathyroidism?
|
secondary
|
|
|
MCC of hyperparathyroidism?
|
parathyroid adenoma (80%)
|
|
|
2nd MCC of hyperparathyroidism?
|
parathyroid hyperplasia
|
|
|
parathyroid hyperplasia is seen in?
|
MEN types I and II
|
|
|
familial hypocalciuric hypercalcemia (FHH) is due to a mutation in?
|
the Ca++ receptor
|
|
|
effects of chronic Li use on the parathyroid?
|
alters Ca++ sensing and promotes parathyroid cell hyperplasia
|
|
|
parathyroid carcinoma (although rare) commonly involves a mutation in?
|
Rb gene
|
|
|
what would the PTH levels be in FHH or lithium use?
|
high
|
|
|
how would the 24 hr. urine Ca++ levels tell us if FHH was the cause of our hypercalcemia?
|
FHH is indicated if the calcium/creatinine clearance ratio is <0.01
|
|
|
treatment of acute, severe hypercalcemia
|
* rehydration with normal saline
* pamidronate or zolendronate(bisphosphonates) * prednisone |
|
|
treatment of chronic hypercalcemia?
|
*surgery (parathyroidectomy) is only effective therapy
|
|
|
indications for parathyroidectomy?
|
*hypercalcemia symptoms
*kidney stones *osteoporosis *serum Ca++>1 mg/dl above normal *age<50 |
|
|
is FHH an indication for a parathyroidectomy?
|
NO
(has not been shown to be effective) |
|
|
non-operative management of hypercalcemia?
|
*adequate hydration
*moderate Ca++ intake *avoid diuretics, lithium *oral phosphonates |
|
|
how often is a patient with chronic hypercalcemia assessed?
|
*serum Ca++ and creatinine yearly
*DEXA every 1-2 yrs |
|
|
what would the PTH and Ca++ levels be like in secondary hyperparathyroidism?
|
PTH - high
Ca++ - low or normal |
|
|
phosphate, vitamin D and calcium levels in secondary hyperparathyroidism due to chronic renal failure?
|
phosphate - high
calcium - low vit. D - low |
|
|
treatment of secondary hyperparathyroidism due to chronic renal failure?
|
*correct hyperphosphatemia (dietary restriction, phosphate binders)
*Ca++ supplementation *vitamin D analogs *calcimimetics (cinacalcet) *parathyroidectomy as last resort if symptomatic |
|
|
where is hypocalcemia commonly seen?
|
*ICU patients
*ESRD |
|
|
clinical s/s of hypocalcemia?
|
*parasthesias
*seizures *muscle spasms *mental changes *cataracts *dry skin, brittle hair and nails *abnormal dentition |
|
|
triad seen in polyglandular autoimmune syndrome type 1?
|
"HAM syndrome"
*hypoparathyroidism, adrenal insufficiency, mucous candidiasis |
|
|
mechanism behind hypomagnesemia causing hypoparathyroidism?
|
Mg+ levels are decreased, this shuts off PTH secretion
|
|
|
what are the levels of Ca++ and PTH in pseudohypoparathyroidism?
|
Ca++ - low
PTH - high (PTH resistance) |
|
|
what are the levels of Ca++ in pseudopseudohyperparathyroidism?
|
normal
|
|
|
drugs that can cause hypoparathyroidism?
|
foscarnet
diuretics antineoplastic agents (Ara-C, cisplatin) antimicrobials (pentamidine, ketoconazole) |
|
|
pancreas abnormality that can cause hypocalcemia?
|
pancreatitis
(soap formation) |
|
|
what is the best lab test to look for vit. D stores and vit. D deficiency?
|
25-OH Vitamin D levels
|
|
|
therapy for acute hypocalcemia?
|
*calcium gluconate
* replete Mg first, otherwise Ca++ will not correct |
|
|
therapy for chronic hypocalcemia?
|
CaCo3 with meals
vitamin D supplement thiazide diuretic (persistant hyperphosphatemia - add Al(OH)3: phosphate binding resin) |
|
|
treatment for severe hypercalcemia due to vitamin D toxicity?
|
prednisone
|
