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362 Cards in this Set
- Front
- Back
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Describe the difference between paracrine, autocrine and endocrine cells.
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Paracrine: cells secreting substances that act on neighboring cells
Autocrine: acts on the secreting cell Endocrine: acts on target cells at a distance |
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Homones can be classified on their composition. What are the three main categories of hormones based on composition?
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1. Tyrosine derivatives
2. Steroids 3. Peptides/Proteins |
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Which categories of hormones are water soluble?
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Tyrosine derivatives
Peptides Proteins |
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How are water soluble hormones released into the bloodstream?
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Like neurotransmitters; need to be synthesized and packaged into vessicles, then released in a Ca-dependent fusion exocytosis
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Which category of hormones is lipid soluble?
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Steroids
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How are steroids released into the blood stream?
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Since they can permeate the membrane, they are synthesized and released as needed
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How are protein/peptide hormones carried in the blood?
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They are carried in their active form without binding to any carrier proteins.
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What causes the short half life of protein/peptide hormones?
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Circulating proteases in the blood
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How are steroid hormones carried in the blood?
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Coupled to hormone-binding proteins (globulins/albumin)
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T/F: The entire steroid hormone/homone-binding protein complex is biologically active.
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False: Only the free hormone is biologically active
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What percentage of steroid hormone exists in its free form at any given time?
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1-5% (not much)
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What are the two methods for measuring hormones in the blood?
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1. Bioassays
2. Immunoassays |
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What are the pros and cons of Bioassays?
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Pros: measures hormone function/activity
Cons: many hormones have same fnxn = may be looking at net effect |
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What are the two types of immunoassays that measure hormones?
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Radioimmunoassay
ELISA |
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What are the pros and cons of immunoassays?
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Pros: good measure of hormone levels
Cons: doesn't not measure activity of hormones/defective hormones |
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What is the main difference in methodology between bioassays and immunoassays?
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Bioassays was an exogenous system (cell lines) to measure; Immunoassays use an endogenous system
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Describe how an ELISA works
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Dish with antibodies to the hormone in question -> add serum hormone to bind to antibodies -> add enzyme to bind to hormone -> measure enzyme level to deduce hormone level
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In general, what is the difference in hormone receptors between protein/peptide and steroid hormones?
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Protein/peptide = hormone receptors in cell membrane bring hormone in
Steroids = pass freely into cell and bind to cytoplasmic or nuclear receptors |
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What are the three types of hormone receptors for protein/peptide hormones?
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1. G-protein-coupled receptors
2. Cytokine receptors 3. EGF Receptors |
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For the following GPCR state its MOA: Gs
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Gs (stimulates) = increased Adenylate Cyclase -> increased cAMP -> increased short term phosphorylation and long term gene expression
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For the following GPCR state its MOA: Gi
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Gi (inhibitory) = decrease andenylate cyclase -> decrease cAMP -> decrease ST and LT actions
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For the following GPCR state its MOA: Gq
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Gq = Activation of Phosphlipase C -> activation of IP3 -> increased IC [Ca] from ER release -> increased ST and LT actions
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What is the main kinase of a cytokine receptor?
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Janus Kinase (JAK): can phosphorylate receptor itself or a bunch of downstream signaling stuff
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What is the main characteristic of an EGF receptor?
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The EGF receptor is a tyrosine kinase itself
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What are the 5 mechanisms that regulate hormone levels?
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1. Feedback mechanisms (mainly negative)
2. Plasma levels 3. Change the effectiveness of the hormone 4. Down regulate the hormone receptors 5. Spare receptors |
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The anterior pituitary is derived from what embryologic feature?
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Thickening of Rathke's pouch (outgrowth of endoderm)
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The posterior pituitary is derived from what structure?
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Extension of the hypothalamus - neural tissue
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Which two structures are mixed endocrine glands, communicating between endocrine and neuronal tissue?
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Pituitary and Adrenal glands
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Which hormones are released by the anterior pituitary?
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FLAT PiG:
FSH LH ACTH TSH Prolactin GH |
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What hormones are released from the posterior pituitary?
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Oxytocin and ADH (vasopressin)
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How could one distinguish between anterior and posterior pituitary on histology?
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Posterior pit has no cell bodies, you will not see nuclei on staining (vs Anterior pit)
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Trace how blood gets to the Anterior pit?
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Superiorhypophyseal a. travels to the a capillary plexus in the median eminence -> portal vein carries blood to another plexus in the anterior pit
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What artery brings blood to the posterior pit?
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inferior hypophyseal
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How do releasing factors from the hypothalamus reach the anterior pit?
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through the capillary plexus of the median emininece
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The adrenal cortex is derived from what embryological tissue?
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Mesenchymal cells
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The adrenal medulla is derived from what embryological cells?
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neural crest cells
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How are hormones in the adrenal medulla regulated?
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synapses from the SNS allow medulla to secrete EPI and NE
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How are hormones in the adrenal cortex regulated?
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regulated by the release of ACTH from the pituitary gland
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What category of hormones are secreted from the adrenal cortex?
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Steroid hormones
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What are the three layers of the adrenal cortex and what hormones are released from each layer?
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Zona glomerulosa - aldosterone
Zona Fasciculata - glucocorticoids (cortisol) Zona Reticularis - Androgens GFR=Salt, Sugar, Sex "The deeper you go, the sweeter it gets" |
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From what embryologic tissue is the pineal gland derived?
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neuronal tissue
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What is the function of the pineal gland?
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1. circadian cycles via melatonin
2. puberty (destruction of pineal gland = early onset puberty) |
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How do hormones from the hypothalamus reach the anterior pituitary?
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Hypothalaic hormones are released by neurons to the median eminence -> released to the hypophyseal portal system -> anterior pituitary
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For the following hypothalamic hormones state which pitutiary hormone it activates/inhibits:
TRH GHRH Somatostatin GnRH CRH PIH |
TRH -> TSH
GHRH -> GH Somatostatin -> inhibits GH GnRH -> FSH, LH CRH -> ACTH PIH -> inhibits prolactin |
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All hormones secreted from the hypothalamus are peptide hormones except which one?
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PIH is dopamine
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Which hypothalimic hormones couple to Gs receptors?
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TRH, GHRH, GnRH, CRH
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Which hypothalimic hormones couple to Gi receptors?
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Somatostatin and PIH
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Which hypothalimic hormones couple to Gq receptors?
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GnRH
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The anterior pituitary (adenohypophysis) has approximately what percentage of lactotrophs (secreting PRL)?
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30%
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What is the main site of action of PRL?
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mammary gland
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Under what category of receptors do PRL receptors belong?
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growth hormone/cytokine receptor family
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In general, what is the MOA of PRL receptor binding?
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dimerization of receptors -> activation of JAK/STAT pathway
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What is a primary endocrine disorder?
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One that arises from a dysfunction in the target organ (e.g., adrenals, thyroid)
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A secondary endocrine disorder arises from what organ?
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Pituitary
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A tertiary endocrine disorder arises from what organ?
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hypothalamus
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Prolactin-secreting adenocarcinomas results in what symptom?
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hyperprolactinemia
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What pharmacological therapy is used to shrink pituitary prolactin-secreting adenomas?
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Bromocriptine, a DA agonist
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What causes Sheehan's Syndrome and what is it's first presenting symptom?
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diminished PRL secretion from hemorrhagic trauma to the pituitary during delivery; failure of lactation is the first symptom
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What are the three main metabolic actions of GH?
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1. increased serum glucose (via gluconeogenesis and insulin resistance)
2. increased amino acid uptake -> protein synthesis 3. increased hormone sensitive lipase -> FFA synthesis |
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What are the four main growth actions of GH?
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1. increases cell size
2. increases cell number 3. increases long bone growth prior to puberty 4. increase in appositional bone growth post-puberty |
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Insulin Growth Factor (IGF) requires GH and what other hormone?
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Insulin
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Once GH reaches its set point what hypothalamic hormones are inhibited/stimulated?
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GHRH is inhibited
Somatostatin is stimulated -negative feedback loop |
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What two metabolites stimulate GH?
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increased amino acids
decreased blood sugar (hypoglycemia) |
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What is the fate of IGF in a pure carbohydrate diet?
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Carbs only -> decreased GH + increased insulin = no IGF
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What is the fate of IGF in a mixed diet?
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Mixed diet -> high GH + high insulin = IGF
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What is the fate of IGF in prolonged starvation?
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Starvation -> high GH + low insulin = no IGF
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What two syndromes are a result of hyper GH secretion during prepuberty?
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Gigantism (increased long bone growth)
Delayed puberty (high GH inhibits GnRH) |
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What syndrome results from hyper secretion of GH post-puberty?
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acromegaly (growth of appositional bones: jaw, hands, feet)
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What are the effects of hyposecretion of GH during prepuberty?
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Dwarfism: either reduced GH levels, reduced GH receptors, or normal GH fnxn but reduced IGF fnxn
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What are the effects of hyposecretion of GH post-puberty?
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No dramatic effect; slight hypoglycemia
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what is the most sensitive growth factor stimulated by GH?
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IGF-1 (insulin-like growth factor
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GH deficiency is characterized by what sx?
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central obesity
reduced muscle mass reduced bone mass reduced quality of life |
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What is the primary cause of excessive GH production?
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GH secreting pituitary tumors
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For the following hormone state (1) the target gland/organ, (2) stimulator, (3) suppressor, (4) cause of excess, and (5) cause of deficiency:
ACTH |
1. Adrenal gland
2. CRH 3. Cortisol (neg feedback on ACTH and CRH) 4. hypersecretion at the pituitary or adrenal gland 5. impaired pituitary ACTH secretion or defective cortisol production` |
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For the following hormone state (1) the target gland/organ, (2) stimulator, (3) suppressor, (4) cause of excess, and (5) cause of deficiency:
TSH |
1. Thyroid
2. TRH from hypothalamus 3. TH and SST inhibit at the level of the pituitary 4. Hypothyroidism and hyperpituitarism 5. Hyperthyroidism and hypopituitarism |
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For the following hormone state (1) the target gland/organ, (2) stimulator, (3) suppressor, (4) cause of excess, and (5) cause of deficiency:
GH (somatotropin) |
1. Liver
2. GHRH 3. GH, somatomedins, Dopamine analogs, somatostatins 4. GH secreting pituitary tumors 5. defects of the hypothalamus, pituitary or at the receptors on the target organ |
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For the following hormone state (1) the target gland/organ, (2) stimulator, (3) suppressor, (4) cause of excess, and (5) cause of deficiency:
PRL |
1. Breast
2. TRH (thyrotropin releasing hormone) 3. Prolactin, Dopamine (PIH) 4. breastfeeding, estrogens and psychotropic drugs, PRL-producing pituitary tumors, hypothyroidism 5. |
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What are the criteria to determine when GH is non-suppressible?
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If the GH levels are > 2mg/ml 1 hour after a 100 OGTT
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What is the most important physiological reason for hyperprolactinemia?
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breastfeeding in the postpartum period
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What are the two main clinical sx of hyperprolactinemia?
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1. galactorrhea (presence of milk in a nonpregnant/nonpostpartum state)
2. hypogonadism (amenorrhea, decreased libido) |
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What are the lab values for a PRL secreting tumor?
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serum PRL levels above 100-200ng/ml in a nonpregnant individual
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What are the two locations for problems in cortisol deficiency?
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pituitary or adrenal gland
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What is the difference between Cushing's Syndrome and Cushing's Disease?
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Syndrome: the signs and sx of hypercortisolemia, regardless of cause
Disease: hypercortisolemia from an ACTH-producing pituitary adenoma |
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What percentage of Cushing's Syndrome cases are a result of Cushing's Disease?
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60-80%
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What are the three steps one takes upon the suspicion of Cushing's syndrome?
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1. DST (dexamethasone suppression test) and UFC (urinary free cortisol) tests
2. Determine ACTH dependency from serum ACTH levels 3. If ACTH-dependent (=tumor) resect tumor with transsphenoidal resection |
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Pituitary apoplexy presents with what sx?
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sudden onset of: headache, visual changes, opthalmoplegia and altered mental status
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What is the cause of pituitary apoplexy?
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sudden hemorrhage or infarct of the pituitary gland
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What tests are used to measure GH secretion?
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Best: combined Arginine-GHRH stim test
Insulin stim test |
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What tests are used to measure PRL secretion?
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TRH to stim PRL
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What tests are used to measure secretion of TSH?
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TRH to stimulate TSH
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What tests are used to measure secretion of LH,FSH?
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GnRH to stim LH,FSH - BUT NOT HELPFUL DUE TO WIDE RANGE OF NL RESPONSES OVERLAPPING WITH HYPOPITUITARISM
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What tests are used to measure secretion of ACTH?
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Insulin
CRH Metyrapone CRH TEST IS NOT YET WELL STANDARDIZED IN HYPOPITUITARISM |
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Clinical syndromes of posterior pit dysfunction are primarily associated with disorders of what hormone?
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AVP (arginine vasopressin = ADH)
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What are the main causes for overproduction and underproduction of AVP?
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Overproduction: SIADH
Underproduction: Diabetes Insipidus (central or nephrogenic) |
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What are the most common hypersecretory tumors of the pituitary?
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prolactinomas (30-40%)
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Which adenomas typically present with visual changes or hypopituitarism but not hypersecretory syndrome?
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"Nonfunctioning" pituitary adenoma
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When would you give Semorelin vs. Somatropin/Somatrem in a case of GH deficiency?
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Semorelin, a GHRH stimulating drug is only effective if the GH deficiency is from the hyppothalamus
Somatropin/Somatrem are recombinant GH and work more effectively and work for both hypothalamic and pituitary secretion problems |
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Which somatostatin analog has a longer half life than somatostatin and preferentially inhibits GH over insulin?
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Octreotide
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In tumors that secrete both PRL and GH causing acromegaly, what may be a good pharm-therapeutic option?
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DA receptor agonists: Bromocriptine, Cabergoline
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What are the therapeutic uses for PRL?
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There are no therapeutic uses for PRL
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Which hormones from the pituitary stimulate the testes and ovaries?
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FSH/LH
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Which hormone from the hypothalmus stimulates the prdxn of FSH/LH?
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GnRH
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What inhibitory substances secreted from the ovaries and testes acts solely on the pituitary?
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Inhibins
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What inhibitory substances secreted from the ovaries and testes acts on both the pituitary and hypothalamus?
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the sex steroids: testosterone, estrogen, progesterone
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From where in the hypothalums is GnRH secreted?
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the Arcuate and Preoptic nuclei
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What is the rate-limiting step in the synthesis of the sex steroids?
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the conversion of cholesterol to pregenalone
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POMC is the prohormone of what hormone from the anterior pit?
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ACTH
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What is the enzyme responsible for the cleaving of the cholesterol side chain to produce pregnenalone?
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Desmolase or 20,22-desmolase
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How many carbons are in the followning sex steroids:
estrogens androgens progestins |
estrogens - 18
androgens - 19 progestins - 21 |
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What membrane receptors are on granulosa cells?
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FSH
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What membrane receptors are on Theca cells?
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LH
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Granulosa cells and theca cells are located where?
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granulosa cells surround the oocyte and theca cells circle the oocyte in the interstital space
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Explain the 2 cell theory of sex steroid production in female reproduction.
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Granulosa cells cannot convert progesterone to androstenedione and theca cells cannot take testosterone to estradiol so...granulosa cells convert cholesterol to progesterone which is carried to the theca cell to make adrostenedione then it is carried back to the granulosa cell to produce testosterone and eventually estradiol.
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Explain the 2 cell theory of sex steroid production in male reproduction.
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Sertoli cells cannot make testosterone so this is done in the Leydig cell. Leydig cells cannot convert testosterone to estradiol (no aromatase) so testosterone is sent to the sertoli cell and converted to estradiol
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What is the chronology of anterior pit hormone deficiency?
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GH -> FSH/LH -> TSH -> ACTH
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Moving toward the adrenal medulla, state (1) the name of the cortical layer and (2) the major hormone produced there
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Zona Glomerulosa - aldosterone
Zona Fasiculosa - Cortisol Zona Reticulosa - Adrogens (DHEA-S) |
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What is the rate limiting step in steroidogenesis?
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the conversion of cholesterol to pregnenalone by 20,22 desmolase
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Name the precursors for the following steroids produced in the adrenal cortex:
1. Aldosterone 2. Cortisol 3. Testosterone |
1. pregnenalone
2. 17-hydroxypregnenalone 3. adrostenedione |
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What are the primary electrolytes controlled by aldosterone?
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Na - retention
K - excretion |
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Hyperaldosteronemia is characterized by what electrolyte imbalances?
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Hypernatremia
Hypokalemia |
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How are aldosterone levels controlled in the body?
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Renin-Angiotensin system
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What is the hallmark of prolonged cortisol release due to prolonged stress?
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muscle weakness
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What does it mean to say that cortisol has "permissive effects"?
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cortisol increases the efficiency of other hormones that are needed to mobilize resources in times of stress
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What are the effects of cortisol on glucose?
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increases serum glucose by:
1. increasing gluconeogenesis 2. increasing insulin resistance |
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What are the effects of cortisol on FFA?
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increases serum FFA by:
1. moving fat to centripetal distribution 2. increasing the efficacy of EPI -> stimulation of HSL -> TG's to FFA |
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What are the effects of cortisol on bone?
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Cortisol decreased Vitamin D -> decreased Ca absorption -> osteoporosis/osteopenia
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What are the effects of cortisol on cardiovascular function?
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increases B-adrenergic receptors and EPI efficacy -> increased HR and contractility
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What are the effects of cortisol on muscles?
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Cortisol causes proteolysis -> frees up amino acids to go to liver -> gluconeogenesis
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What are the effects of cortisol on connective tissue?
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decreased proliferation of fibroblasts -> thin skin, bruising
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What are the effects of cortisol on prostaglandin synthesis?
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cortisol decreases prostaglandin synthesis by blocking the effects of Phospholipase A2 which creates arachadonic acid
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Why is cortisol never used for treatment of external wounds?
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Cortisol inhibits prostaglandin formation as well as decreases fibroblast production -> wounds cannot heal -> increased infection
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What is the mechanism by which excess ACTH production leads to hyperpigmentation?
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ACTH's prohormone, POMC, contains a-MSH (melanin stimulatin hormone)that is initially bound to ACTH before activation of the free hormone. When you make too much ACTH, you inadvertantly make too much MSH as well -> hyperpigmentaiton.
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To what type of GPCR does ACTH bind in the adrenal cortex?
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Gs -> increases cAMP
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What is the only hormone released from the adrenal glands that regulates ACTH?
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Cortisol
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Explain the general mechanism for cortisol action on its target cell.
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Cortisol freely crosses membrane -> binds to monomer/dimer HSP70 receptor in cytosol -> dimer enters the nucleus and effects gene expression
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Relative to epinephrin, how long does it take for cortisols effects to manifest?
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LONG. Minutes to hours to days (vs the immediate effects of EPI)
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What are hormone responses to Addison's Dz?
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1. low Cortisol
2. low Aldo 3. high ACTH due to loss of negative feedback |
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What is the cause of Addison's Dz?
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Autoimmune destruction of the entire adrenal gland
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What are the adrenal hormone responses to hypopituitary dysfunction?
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1. low ACTH
2. low cortisol no affect on Aldo |
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What are the effects on adrenal homone secretion in hypersecretory adrenal tumors?
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1. high cortisol with low ACTH
2. high Aldo |
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What are the effects on the adrenal hormones from hypersecretory pituitary tumors?
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1. high ACTH
2. high Cortisol 3. normal aldo |
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A pt presents with moon facies, supraclavicular fat deposits and purple striae on the abdomen. His serum showed low ACTH, high cortisol and normal aldo. What is the most likely cause for his hypercortisolemia?
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exogenous corticosteroid use
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What hormones are produced in the adrenal medulla?
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EPI and NE (lesser amounts)
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Which cells in the adrenal medulla secrete EPI?
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chromaffin cells
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What stimulates the chromaffin cells to secrete EPI?
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postsynaptic SNS from the splanchnic nerve
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Describe the mechanism for the release of EPI from chromaffin cells
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NACh receptor opens -> opening of VG CA channels -> increases IC [Ca] -> Ca-dependent fusion of EPI vessicles to the membrane followed by exocytosis
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What is the MOA producing the symptoms of a pheochromocytoma?
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A mutation in the Ret receptor on chromaffin cells causes a constantly active receptor -> increase in cell growth (tumor) and increase in catecholamines (HTN, diaphoresis, palpitations)
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Stimulation of a-1 adrenergic recpetors causes what sx?
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vasoconstriction/HTN
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Stimuation of the B-1 adrenergic receptors causes what sx?
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increased contractility of the heart and increased HR -> diaphoresis
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Stimulation of the B-2 adrenergic receptors causes what sx?
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vasodilation in muscle beds
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What may a pheochromocytoma present like that would need to be ruled out of your diagnosis?
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anxiety/panic disorder; all others in the differential can be discerned from a patient hx
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Why is it important to always make a biochemical dx before anatomic localization (imaging)?
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The majority of tumors will be nonfunctioning. No need to try and treat a tumor that isn't causing any of the problems.
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What is the gold standard in testing for a diagnosis of pheochromocytoma?
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24 hr urine collection while experiencing symptoms
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90% of pheochromocytomas are unilateral adrenal tumors. How else can they present?
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10% rule:
10% bilateral adrenal 10% extra adrenal 10% malignant 10% come back after surgery |
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What is the course of treatment for a pheochromocytoma?
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Adrenergic blocker: alph-blocker before a beta blocker to avoid severe HTN
Surgery once BP is controlled |
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Primary hyperaldosteronism (Conn's Syndrome) displays what symptoms?
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HTN, hypokalemia - usually in a very young age
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Explain the mechanism behind the hormone abnormalities in Conn's syndrome?
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An aldosterone secreting adrenal tumor secretes too much aldo and turns off Renin-angiotensin system -> high aldo and low renin
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What should the Renin:Aldo be to diagnose Conn's syndrome? PRA level?
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>20 with an Aldo of at least 15
PRA (plasma renin activity) < 2ng/ml/hr |
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What are the treatment options for Conn's syndrome?
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Surgery if a unilateral lesion > 1cm
GRA is treated with glucocorticoid replacement IHA is treated with aldosterone antagonist |
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What hormone released from the hypothalamus is used diagnostically to differentiate between Cushing's syndrome and ectopic ACTH-producing cells?
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CRH (corticotropin-releasing hormone)
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What is the MOA of ACTH?
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G-protein -> increased cAMP -> stimulates the conversion of cholesterol to pregnenalone
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What is the prefered treatment for a diagnosis of adrenal insufficiency?
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Cosyntropin, a synthetic human ACTH
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When are the highest levels of GH released in the system?
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When you sleep
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What is the MOA of somatotropin and somatrem?
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induce the release of IGF-1 which is responsible for GH-like actions
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For whom are somatotropin and somatrem useful?
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treatment of GH deficiency in children
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Somatotropin and somatrem are contraindicated in which individuals?
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should not be used in individuals with closed epiphyses or an enlarging intracranial mass
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Somatostatin and octreotide inhibit what other substances aside from GH?
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insulin, glucagon, gastrin
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Ocreotide and somatostatin are used for the treatment of what condition?
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Acromegaly caused by hormone-secreting tumor
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GnRH is administered for the treatment of what condition?
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GnRH is used to stimulate gonadal hormonal production in hypogondism
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What are the benefits of octreotide over somatostatin?
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longer half-life
specific for GH over insulin |
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What is the MOA of Pegvisomant?
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GH antagonist: binds to the GH receptor
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What class of drugs are used in the treatment of hyperprolactinemia?
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Dopamine receptor agonists: Bromocriptine and cabergoline, most commmon
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What is the only indicated use of oxytocin?
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Obstetrics: to stimulate uterine contraction to induce/reinforce labor and to induce "milk let-down"
|
|
|
What is vasopressin (ADH/AVP/WTF)used for clinically?
|
treatment of diabetes insipidus
|
|
|
What are the major toxicities with vasopressin?
|
water intoxication and hyponatremia
|
|
|
What are the advantages of desmospressin (DDAVP) over vasopressin?
|
minimal activity at the V1 so there are less vasopressive effects
|
|
|
What is the route of administration for DDAVP?
|
nasal spray
|
|
|
What test is used to diagnose Addison's dz?
|
Corticotropin stimulation test
|
|
|
What drug is given to treat Addison's dz?
|
Hydrocortisone
|
|
|
Why must hydrocortisone be administered 2/3 -morning and 1/3-afternoon ?
|
To mimic the daily hormone levels resulting from the circadian rhythm exhibited by cortisol
|
|
|
What is the second line of pharmacotherapy for Addison's if mineralcorticoids cannot be raised properly?
|
fludrocortisone
|
|
|
What is the recommended therapy for secondary and tertiary adrenocortical insufficiency?
|
same as that for primary: hydrocortisone
|
|
|
what test is used to dx the cause of a pt's Cushing's Syndrome?
|
Dexamethasone suppression test: suppresses cortisol in individuals with pit-dependent Cushing's but does not suppress cortisol from adrenal tumor
|
|
|
State the three main mechanisms by which glucocorticoids relieve inflammatory symptoms?
|
1. increased concentration of neutrophils while inhibiting lymphocytes
2. decreased production of prostaglandins and leukotrienes (main mechanism) 3. reduction in the amount of histamine released from basophils and mast cells |
|
|
What is the only glucocorticoid that has no effect on the fetus during pregnancy?
|
Prednisone (fetal liver cannot convert the prodrug to prednisolone and any prednisolone in the mother's circulation is bioconverted back to prednisone in the fetus)
|
|
|
Why must corticosteroids be tapered off gradually?
|
the abrupt removal causes an acute adrenal insufficiency syndrome that can be lethal
|
|
|
Which drug has a longer half-life: prednisone or dexamethasone?
|
Dexamethasone - it is essentially unmetabolized
|
|
|
Thyroid follicular cells synthesize what hormone?
|
TH (it also synthesizes thyroglobulin to which TH will bind)
|
|
|
Thyroid parafollicular cells synthesize which hormone?
|
calcitonin
|
|
|
What is the ratio of iodine in the blood to the follicular cell?
|
1:30
|
|
|
What does the structure of TH look like?
|
2 tyrosine residues iodinated and joined together by an ether link
|
|
|
In the synthesis of TH, how does iodide enter the follicular cell?
|
Active transport: I goes in via an I/Na cotransporter. Then Na is exchanged for K via NA/K ATPase pump
|
|
|
What is the name of the lumenal membrane protein to which I binds, thereby becoming active and ready to attach to TH?
|
thyroperoxidase (TPO)
|
|
|
What percentage of trapped iodide will eventually become part of TH?
|
95%
|
|
|
Describe the pathway from synthesis to exocytosis of thyroglobulin in the follicular cell?
|
1. TG synthesized in the ER of the cell
2. TG goes to the Golgi where it is packaged and exocytosed 3. TG in the lumen in such high qtys that it is in colloid form |
|
|
What enzyme forms the bond between Tyr and I?
|
Thyroperoxidase (TPO)
|
|
|
What is the mechanism by which [T3]TG becomes free hormone?
|
TG becomes endocytosed and taken up by lysosomes; Lysosomes degrade TG to release T4, T3, RT3 as well as MIT and DIT remnants
|
|
|
What molecule carries TH to its target?
|
Thyroxine-binding globulin (TBG)
|
|
|
Why may a T3 or T4 assay be unhelpful in diagnosing thyroid disorders?
|
Approximately 99% of T3 and T4 are in bound form (inactive); assays would show a lot of total TH but very small qtys of free TH
|
|
|
T3 is the more potent TH. What happens to T4 when it reaches its target?
|
T4 becomes deionidated to T3
|
|
|
Where are most receptors for TH located?
|
In the nucleus of the target cell
|
|
|
What is the net effect of TH on target cells?
|
an increase or decrease in gene expression, depending on the type or TH response element
|
|
|
What are the two main functions of TH?
|
1. Control of basal metabolic rate
2. Growth, Development, differentiation |
|
|
An increase in T3 has what effect on BMR?
|
It increases catabolic mechanisms (the other one is the other one)
|
|
|
What hormone is responsible for the majority of brain development postnatally?
|
TH
|
|
|
Describe the hypothalamus -> Pituitary -> thyroid axis
|
TRH -> TSH -> TH
|
|
|
What molecule inhibits the formation of TH?
|
Negative feedback: T3 and T4 down regulate TRH receptors in the anterior pituitary thereby decreasing the secretion of TSH
|
|
|
What is the pathway by which TSH stimulates the synthesis of TH?
|
G-protein (Gs) -> increase in cAMP
|
|
|
What are the four main effects of TSH on the thyroid?
|
1. increase in follicular cell number
2. increase the synthesis of thyroperoxidase and thyroglobulin 3. increases iodide uptake 4. increased organification of iodide |
|
|
Which three conditions are associated with Hyperthyroidism?
|
1. Grave's Disease
2. Tumors of the Pituitary or thyroid 3. excess TH administration (wt loss) |
|
|
Why is T3 considered the active form of TH?
|
The affinity of the TH receptor is 10 fold greater for T3 than T4
|
|
|
What may be the fate of a neonate with low TH levels who is not screened at birth?
|
sporadic cretinism
|
|
|
What two factors influence the amount of serum T4?
|
1. Function fo the pit-thyroid axis
2. amount of circulating TBG |
|
|
What factors can increase the amount of circulating TBG, thereby increasing the serum T4?
|
pregnancy and estrogen excess
|
|
|
What are the most valid and important assessments of thryroid function?
|
Serum TSH levels
|
|
|
What does a high TSH suggest?
|
Inadequate thyroid hormone production
(the other one's the other one) |
|
|
What are the normal range values for serum TSH?
|
0.5 - 5.0 microU/mL
|
|
|
What syndrome is evidence that the conversion of T4 to T3 or RT3 is under metabolic control?
|
Euthyroid sick syndrome: in chronic illness or starvation, T4 seems preferentially inactiviated to RT3 rather than activated to T3
|
|
|
What are the 7 most common causes of hyperthyroidism?
|
1. Grave's Disease
2. Factitious/Iatrogenic 3. Toxic Adenoma (Hot Nodule) 4. Toxic Nodular Goiter 5. Subacute Thyroiditis 6. Silent Thyroiditis 7. TSH-secreting Pit tumors |
|
|
What will the RAI uptake show in a case of factitious/iatrogenic thyrotoxicosis?
|
the RAIU will be close to zero
|
|
|
How will a thyroid with toxic adenoma appear?
|
A solitary nodule in the gland with shrinkage in the surrounding glandular tissue due to the overpdxn of TH by the nodule supressing the TSH
|
|
|
What is the cell mutation in 10-40% of toxic adenomas?
|
mutation in the G protein domain rendering the TSH receptor active without TS-activating G-proteins and cAMP
|
|
|
What causes subacute thyroiditis?
|
prior viral URI
|
|
|
What are the symptoms of subacute thyroiditis?
|
painful, swollen thyroid; fever; high sedimentation rate
|
|
|
The postpartum period is susceptible to what form of hyperthyroidism?
|
Silent thyroiditis
|
|
|
Which is the suspected etiology of silent/postpartum thyroiditis?
|
autoimmune
|
|
|
What is the most common form of primary hypothyroidism?
|
Hashimoto's thyroiditis
|
|
|
What is detectable in the serum of a pt with Hashimoto's thyroiditis?
|
anti-TPO (thyroid peroxidase antibodies)
|
|
|
For the following hyperthiroid disease, state the relative values for (1) T4, (2) free T4, (3) T3, (4) RAIU, (5) TSH as well as (6) treatment: Factitious
|
T4: high
Free T4: high T3: high RAIU: zero TSH: low Treatment: stop excess TH |
|
|
For the following hyperthyroid disease, state the relative values for (1) T4, (2) free T4, (3) T3, (4) RAIU, (5) TSH as well as (6) treatment: Hot Nodule
|
T4:high
Free T4: high T3: high RAIU: high TSH: low Treatment: surgery, RAI |
|
|
For the following hyperthyroid disease, state the relative values for (1) T4, (2) free T4, (3) T3, (4) RAIU, (5) TSH as well as (6) treatment: Toxic Nodular Goiter
|
T4: high
Free T4: high T3: high RAIU: nl to high TSH: low Treatment: surgery, RAI |
|
|
For the following hyperthyroid disease, state the relative values for (1) T4, (2) free T4, (3) T3, (4) RAIU, (5) TSH as well as (6) treatment: subacute thyroiditis
|
T4: high
Free T4: high T3: high RAIU: low TSH: low Treatment: NSAIDS and time |
|
|
For the following hyperthiroid disease, state the relative values for (1) T4, (2) free T4, (3) T3, (4) RAIU, (5) TSH as well as (6) treatment: Silent thyroiditis (PPT)
|
T4: high
Free T4: high T3: high RAIU: low TSH: low Treatment: time; steroids |
|
|
For the following hyperthyroid disease, state the relative values for (1) T4, (2) free T4, (3) T3, (4) RAIU, (5) TSH as well as (6) treatment: Graves' disease
|
T4: high
Free T4: high T3: high RAIU: high, diffuse TSH: low Treatment: RAI, drugs, surgery |
|
|
For the following hyperthiroid disease, state the relative values for (1) T4, (2) free T4, (3) T3, (4) RAIU, (5) TSH as well as (6) treatment: T3 toxicosis
|
T4: nl
Free T4: nl T3: high RAIU: high TSH: nl to low Treatment: |
|
|
For the following hyperthiroid disease, state the relative values for (1) T4, (2) free T4, (3) T3, (4) RAIU, (5) TSH as well as (6) treatment: TSH over-production
|
T4:high
Free T4: high T3:high RAIU: high TSH: high Treatment: surgery, RAI |
|
|
For the following hyperthiroid disease, state the relative values for (1) T4, (2) free T4, (3) T3, (4) RAIU, (5) TSH as well as (6) treatment: Struma ovarii
|
T4: high
Free T4: high T3: high RAIU: high in pelvis TSH: low Treatment: ovarian surgery |
|
|
For the following hyperthiroid disease, state the relative values for (1) T4, (2) free T4, (3) T3, (4) RAIU, (5) TSH as well as (6) treatment: Jod-Basedow
|
T4: high
Free T4: high T3: high RAIU: high TSH: low Treatment: time |
|
|
What is the most common condition causing mental retardation for which nationwide screening is done?
|
CHT - congenital hypothyroidism
|
|
|
Name the 5 enzymes or proteins that may be defective in CHT?
|
1. Na/I symporter
2. Pendrin (transports I to the surface of follicular membrane) 3. TPO (thyroperoxidase) 4. Thyroglobulin (Tg) 5. Iodotyrosine deiodinase |
|
|
What is the most common etiology of permanent CHT?
|
85% is due to a lack of normal thryroid gland formation or migration (thyroid dysgenesis)
|
|
|
What is the pattern of inheritance of thyroid dysgenesis?
|
None. The mutation is sporadic
|
|
|
What is the primary screening tool for CHT?
|
T4 via heel stick
|
|
|
Why is it important to have a confirmatory second CHT test at approx 1-2 weeks of life?
|
A TSH surge occurs upon cutting the umbilical cord which diminishes over about 10 days. APPROX 20% OF CHT IN COLORADO IS DETECTED ON SECOND SCREEN
|
|
|
For how long should you treat a POSSIBLE diagnosis of CHT?
|
Treat at least for th first 2.5 - 3 yrs of life, when cerebral development is thought to be complete
|
|
|
What is the standard treatment for CHT?
|
LT4
|
|
|
What food source interferes with Lt4 absorption and should therefore be avoided at the time of dosing?
|
soy protein
|
|
|
What appears to be one of the main causes of transient CHT in areas of endemic hypothyroidism?
|
maternal iodine deficiency
|
|
|
What is the average weight of a normal thyroid?
|
20 gm
|
|
|
What is the most common benign tumor of the thyroid?
|
Follicular/Hurthle cell adenoma
|
|
|
What is most common malignant tumor of the thyroid?
|
Papillary carcinoma
|
|
|
T/F: Anaplastic carcinoma of the thyroid is the most aggressive, but one of the more rare malignant tumors
|
True (<5% occurance)
|
|
|
Medullary carcinoma of the thyroid is associated with what familial syndrome?
|
MEN types IIa and IIb (III)
|
|
|
From which thyroid cells do medullary carcinomas arise?
|
C-cells
|
|
|
What distinguishes a follicular adenoma from a follicular carcinoma microscopically?
|
adenoma: variable sized follicles confined within the capsule
Carcinoma: follicle invade capsule and vasculature |
|
|
What is the prognosis for a papillary carcinoma?
|
Excellent prognosis due to slow growth.
|
|
|
What microscopic feature is pathognemonic for papillary carcinoma?
|
Nuclear clearing: "Orphan Annie Eyes" formed from the pushing of chromatin to the periphery of the cell
|
|
|
Medullary carcinoma of the thyroid usually presents with high serum levels of which hormone?
|
calcitonin
|
|
|
What are the three morphologic patterns exhibited in anaplastic carcinoma?
|
spindled
giant cell squamoid |
|
|
What other thyroid illness predisposes one to thyroid lymphoma?
|
Hashimoto's Thyroiditis
|
|
|
What is the most common type of thyroid lymphoma?
|
B-cell lymphoma
|
|
|
Which type of nodule (hot v. cold) is more common?
|
cold
|
|
|
T/F: thyroid nodules have a high risk for malignancy if they are overactive?
|
False: overactive nodules (hot nodules) are at a low risk for malignancy
|
|
|
What is the next step in a clinical work-up of a pt with an asymptomatic thyroid nodule and a normal TSH?
|
Fine Needle Aspiration (FNA)
|
|
|
What will be the histological appearance of a benign thyroid nodule?
|
honeycomb appearance, pale stain with cracking artifact (colloid)
|
|
|
What percentage nodules tested with FNA will end up being benign?
|
80/20 rule
80% benign |
|
|
Approximately 50% of thyroid nodules are associated with which mutated protein?
|
Ras
|
|
|
Papillary thyroid cancer, the most common kind of thyroid cancer, harbors a mutation on chromosome 10--activating which tyrosine kinase protein?
|
RET (normally not expressed)
|
|
|
anaplastic carcinoma, the most aggressive form of thryroid cancer is associated with a mutation in what gene?
|
p53
|
|
|
40% of thyroid cancers are associated with a mutation in which protooncogene?
|
BRAF
point mutation causing uncontrolled activation of MAP kinase signalling |
|
|
What hormone stimulates the release of TSH?
|
TRH from the hypothalamus
|
|
|
What factors can inhibit the release of TSH?
|
TH, somatostatin, dopamine and glucocorticoids?
|
|
|
What is the major regulated step in the synthesis of THs?
|
the uptake of iodide.
Stimulated by TSH (via GPCR) and blocked by anions of similar size (SCN-, ClO4) and high levels of iodide itself (decreases expression of transporters) |
|
|
What is the consequence of Levothyroxine's narrow therapeutic window?
|
one must pay particular attention to the pharmacokinetics and drug-drug interactions
|
|
|
Where is LT4 best absorbed?
|
ilieum and colon
|
|
|
T/F: LT4 must be taken on an empty stomach, preferably 4-6 hours after any interacting drugs.
|
True
|
|
|
What drugs can inhibit the deiodination of T4 in the liver?
|
Glucocorticoids
B-blockers Amiodarone PTU |
|
|
What conditions inhibit the deiodination of the T4 in the liver?
|
acute and chronic illness
caloric deprivation malnutrition fetal/neonatal period |
|
|
What are the half-lives of T4 and T3, respectively?
|
T4 = 7 days
T3 = 1 day |
|
|
Synthetic T3 is not advised for patients with what other illness?
|
cardiac disease
|
|
|
Thyroid USP (Armour Thyroid) is formed from what animal thyroid extract?
|
Pigs
|
|
|
What is the rule of conversion from LT4 to Armour Tyroid?
|
100mcg LT4 = 60mg Armour Thyroid
|
|
|
Why must pregnant women with hypothyroidism increase their dosage of LT4
|
elevated estrogen levels will increase levels of TBG
|
|
|
Which two classes of drugs act by interfering with thyroid hormone production?
|
thionamides, iodides
|
|
|
Which two classes of drugs reduce thyroid activity by modifying tissue response (providing symptomatic relief)?
|
b-blockers, corticosteroids
|
|
|
Which two treatments reduce thyroid activity by destroying the thyroid gland itself?
|
surgery
radioactive iodine |
|
|
What are the two main thionamides?
|
Propotyouracil (PTU)
Methimazole |
|
|
Which thionamide does not cross the placenta as easily due to high protein binding?
|
PTU
|
|
|
What is the MOA of thionamides?
|
block the organification and coupling of iodide to TG -> prevents T3/T4 synthesis
|
|
|
What are the most common adverse reactions with thionamides?
|
pruritic rash, gastric intolerance, arthralgias
|
|
|
What is the most dangerous side affect from thionamides?
|
agranulocytosis
|
|
|
What are the age ranges for the three stages of growth?
|
I. conception to 4-6 months of life
II. 4-6 month to adolescence III. Adolescence to final "adult" height |
|
|
In general, what are the etiologies for infants that are Small for Gestational Age (SGA)?
|
imbalances in maternal/fetal environment (placental insufficiency, maternal toxins, acidosis, maternal viral infections, maternal hormonal disorders, genetic disorders, insulin or IGF deficiency)
|
|
|
In general, what are the etiologies for infants that are Large for Gestational Age (LGA)?
|
Excessive insulin of IGF secretion in utero (infants of diabetic mothers)
|
|
|
What proof do we have that GH and TSH are not improtant regulators of fetal growth?
|
infants with documented GH or TH deficiency who are not diagnosed and treated until later in life are NOT born SGA.
|
|
|
What hormone is required for fetal/neonatal brain development?
|
TH
|
|
|
What are the most common causes of variations in height between children?
|
familial short and tall stature
|
|
|
How might one be able to distinguish familial short stature from other conditions of short stature?
|
familial short stature is accompanied by a normal growth rate that is proportional to their mid-zone projected height
|
|
|
In general, what are the causes of poor growth at stage II?
|
malnutrtion
chronic illness metabolic abnormalities |
|
|
What is the difference in grwoth spurts between males and females?
|
Males: growth spurt in the middle of puberty
Females: growth spurt at the onset of puberty |
|
|
Why is serum GH not a useful test for meausring growth hormone deficiency? What should be used instead?
|
GH is released in spurts, so that at any given time you may high or low amounts of GH. IGF-1 or IGFBP3 is a better measure of GH secretion
|
|
|
Under what conditions should one defer treatment of GH?
|
severe mental retardation
life-shortening chromosomal conditions Possible idiopathic or familial short stature |
|
|
T/F: new regulations of supplements require (1) people to report serious ADR to manufacturer w/i 15 days, (2) the company to test for purity, identity and strength, and (3) need to display proof of efficacy and safety on the bottle.
|
False: there is no need to demonstrate proof of efficacy and safety
|
|
|
A label from what organization implies a higher quality supplement?
|
USP
|
|
|
What are the two main physiological roles of calcium in the body?
|
1. structural: major constituent for bone matrix
2. biochemical: excitation-cntraction coupling, stimulus-secretion coupling, blood clotting, membrane excitability, cellular permeability, misc metabolic stuff |
|
|
What are the limits in which Ca must be maintained in the body?
|
8-10mg/dl
|
|
|
What are the limits in which PO4 must be maintained in the body?
|
3-4 mg/dl
|
|
|
What are the three major compartments in which Ca is located?
|
1. Bone - 99% of body calcium
2. intracellular compartment 3. Extracellular compartment |
|
|
What is the three functions of phosphate?
|
1. part of bone matrix
2. intracellular buffer 3. Required for phosphorylation reactions and regulare cellular functions |
|
|
About what percentage of phosphate is free and in the ionized form?
|
85%
|
|
|
What is the net result of PTH actions?
|
increased serum Ca and decreased serum PO4 levels
|
|
|
What three organs determine serum Ca levels?
|
1. bone - remodeling releases both Ca and PO4
2. Kidney - increased Ca rebsorption in distal tubule, decreased PO4 reabsorpion, increased synthesis of 1,25 (OH)2 VitD GI tract: indirect via Vit D--enhances Ca resorbtion |
|
|
How is PTH secretion regulated?
|
Inhibited by fall in free ionized Ca in plssme; inhibited by a rise
|
|
|
In what cells of the parathyroid is PTH synthesized and secreted?
|
Chief cells
|
|
|
C cells, which produce calcitonin, are found in what organ?
|
Thyroid
|
|
|
What stimulates the secretion of calcitonin?
|
increased serum Ca
|
|
|
What is the main function of calcitonin?
|
inhibit bone resorption; cna be used to treat high turnover bone disorders
|
|
|
25-OH Vit D is synthesized in which organ?
|
Liver
|
|
|
The conversion of 25-OH Vit D to 1,25(OH)2VitD in the kidney is catalyzed by which enzyme?
|
1a-hydroxylase
|
|
|
How is 1,25(OH)2 Vit D transported through the blood?
|
bound to trancalciferin
|
|
|
Where is the main site of action for active Vitamin D?
|
in the GI tract
|
|
|
What is the MOA of active Vit D in the GI tract?
|
interacts witha nuclear receptor -> protein synthesis -> increased calcium binding protein -> increases intestinal absorption of Ca (also increases PO4 resorption)
|
|
|
What factors stimulate the synthesis of 1a-hydroxylase and thus 1,25(OH)2 Vit D?
|
decreased serum Ca
decreased serum PO4 increased PTH |
|
|
What is the main hormine that regulates blood Ca in the short term?
|
PTH: mobilizes Ca from bone into blood when Ca levels get too low.
|
|
|
T/F: PTH is under pituitary control.
|
False: parathyroid glans are responsive to plasma [Ca]; decreased Ca stimulates PTH
|
|
|
Describe the process of normal bone remodeling.
|
Osteoclasts bind to the surface ot htte bone and secrete acids to resorb the bone-> creates a resorption pit -> OC signal to osteoblasts who are recruited to fill the pit with bone-forming collagen (osteoid) -> mineralization of new born from a perfect Ca/PO4 product (=24)
|
|
|
When are the two instances in which bone resorption should not equal bone formation?
|
1. Birth-age 20: osteoblast > osteoclast
2. After menopause: osteoclast > osteoblast |
|
|
What is the definition of osteoporosis?
|
Compromised bone strength predisposing one to an increased risk of fragility fracture
|
|
|
What ar the three highest incidence fragility fractures?
|
1. spine
2. hip 3. wrist |
|
|
What is a T score and what does it measure?
|
T score = how many standard deviations below peak bone mass for your age; used to measure the risk of a fragility fracture
|
|
|
What must your T score be to be dx with osteoporosis?
|
< -2.5
osteopenia = -1.0 to -2.5 |
|
|
Why may the T score be an inappropriate measure of fracture risk?
|
The score is only established in postmenopausal women
|
|
|
Why is dietary Ca the best source of Ca intake?
|
Because it is in Ca/PO4 and you need both of these for proper bone formation; supplements usually come in Ca/carbonate form
|
|
|
What are the two pharmacological options for treating Osteoporosis?
|
1. antiresorptive drugs
2. Anabolic agents (stimulate osteoblast activity) |
|
|
Osteomalacia and Rickets are caused by what defect in the bone formation/resorption process?
|
impaired bone mineralization--soft, weak bones
|
|
|
What is the general pathophys behind osteomalacia and rickets?
|
inadequate Ca x PO4 product needed for mineralization of bone
|
|
|
What two classes of disorders are most likely to result in osteomalacia or rickets?
|
Vitamin D disorders
Phosphate Disorders |
|
|
Which Vitamin D is major storage form?
|
25OH Vitamin D
|
|
|
What is the ratio of 25OH Vitamin D to 1,25(OH)2 Vitamin D in the blood?
|
1000:1
|
|
|
Vitamin D-dependent Rickets Type 1 is another name for what Vitamin D disorder?
|
Congenital 1a-hydroxylase deficiency (can't make active Vitamin D)
|
|
|
Vitamin D-dependent Rickets Type II is another name for what Vitamin D disorder?
|
Congenital Vitamin D Receptor deficiency (can make Vit D but it can't bind)
|
|
|
Who is most prone to develop hypophosphatemia from poor oral intake?
|
alcoholics (who else?)
|
|
|
What is the most common cause for congenital rickets?
|
congenital hypophosphatemic rickets
(Vitamin D-resistant rickets) |
|
|
What is the reason for a high alk phos in osteomalacia and rickets?
|
Alk Phos is the byproduct of osteoblast's osteoid formation
|
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What deformities from rickets are noticable on exam?
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bowing of long bones
"rickets rosary" = flaring of the ends of the ribs so they stick out around the sternum |
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What is the treatment for osteomalacia/rickets?
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Calcium
Vitamin D or Calcitriol Phosphate |
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What is Paget's dz?
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excessive unregulated resorption and formation of bone
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40-80% of families with Paget's have a mutation in which gene?
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Squestasome I/p62 (SQSTMI)
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What is the function of SQSTMI?
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a ubiquitin binding protein that forms a scaffold for IL-1 and TNF signalling --> RANK signalling that controls osteoclast differentiation, activity, survival
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The development of Paget's dz requires two things. What are they?
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1. genetic mutation that enhances osteoclast formation/activity
2. paramyxovirus infection that induces change in osteoclast precursors |
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What sign on imaging is pathognemonic for Paget's dz?
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"Blades of Grass" sign in long bone
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Which bone remodeling markers will be elevated in the early phases Paget's Dz?
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NTX (N-telopeptide)
CTX (C-telopeptide) both are markers of osteoclast activity and are present in the early and middle phases |
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Which bone remodeling marker will be elevated in the mid to late phases Paget's Dz?
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Alk Phos, a measure of osteoblast activity
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What do the osteoclasts look like (histology) in a pt with Paget's?
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significant increase in osteoclast # with 20-100 nuclei per cell (nl = 5-10)
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What is the treatment for Paget's Dz?
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Anti-resorptive agents (bisphosphonates, calcitonin)
Analgesics/NSAIDS Corrective surgery |
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What is the calcium conversion in cases of hypoproteinemia?
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Add 0.8 mg/dl to calcium for every 1.0 g/dl decrease in albumin
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What two signs of hypocalcemia are evident on physical exam?
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Chvostek's sign: twitching of the facial muscles with tapping
Trousseau's sign: contraction of the thumb when the blood pressure cuff in on at high pressure |
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What in a pt's PMH allows you to suspect that his hypocalcemia is from autoimmune hypoparathyroidism?
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mucocutaneous candidiasis infection
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What are the lab features of hypoparathyroidism?
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low serum Ca
high serum PO4 low serum PTH |
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What is the treatment for hypoparathyroidism?
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calcium
calcitriol |
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A pt presents to you with muscle weakness/pain, paresthesia in the hands and noticably shortened 4tha nd 5th metacarpals? What illness are you thinking of and what relative lab values would you expect?
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Pseudohypoparathyroidism
Low serum CA high PO4 HIGH PTH |
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Where is the mutation that causes pseudohypoparathyroidism?
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Inactivating mutation in the Gs, alpha subunit (or other PTH response element) -> decrease cAMP -? decrease PTH action
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