Endocrine Flashcards
(283 cards)
1
Q
Thyroid diverticulum arises from the
A
Floor of primitive pharynx and descend into neck
2
Q
Thyroid connected to tongue via
A
Thyroglossal duct – persistence –> thyroglossal duct cyst or pyramidal lobe of thyroid
3
Q
Ectopic thyroid tissue often found on
A
Tongue (removal can –> hypothyroidism if only thyroid tissue)
4
Q
Persistent cervical sinus
A
Branchial cleft cyst in lateral neck
5
Q
Thyroglossal duct cyst
A
Midline in neck that moves w/ swallowing
6
Q
Derivation of thyroid
A
Endoderm
7
Q
Adrenal cortex derivation
A
Mesoderm
8
Q
Adrenal medulla derivation
A
Neural crease
9
Q
Zona Glomerulosa
A
Outer layer – aldosterone (mineralocorticodid), regulated by Ang II
10
Q
Zona fasciculata
A
Middle layer – cortisol (glucocorticoid), reg by ACTH, CRH
11
Q
Zona reticulata
A
Inner layer – androgens – DHEA, reg by ACTH, CRH
12
Q
Medulla
A
Chromafin cells regulated by preganglionic sympathetic fibers –> release catecholamines NE/E
13
Q
Anterior pituitary aka
A
Adenohypophysis
14
Q
Anterior pituitary secretes
A
FSH, LH, ACTH, TSH, PRL, GH, MSH (FLAT PiG)
15
Q
Derivation of anterior pituitary
A
Rathke’s pouch (oral ectoderm)
16
Q
Alpha subunit is common to
A
TSH, LH, FSH, hCG
17
Q
B subunit
A
Determines hormone specificity
18
Q
Acidophils produce
A
GH, PRL
19
Q
Basophiles produce
A
FSH, LH, ACTH, TSH
B-FLAT
20
Q
Posterior pituitary hormones
A
ADH, oxytocin
21
Q
Post pituitary hormone synthesis
A
Synthesis is in hypothalamus in supraoptic/paraventricular nuclei –> post. pituitary via neurophysins
22
Q
Post. pituitary derivation
A
Neuroectoderm
23
Q
Alpha cells of pancreas make
A
Glucagon (peripheral in islet)
24
Q
Beta cells of pancreas make
A
Insulin (central in islet)
25
Delta cells of pancreas make
Somatostatin (interspersed in islet)
26
Insulin synthesis
Preproinsulin from RER --> cleave presignal to proinsulin (stored in secretory granules) --> cleave proinsulin --> exocytose equal amounts of insulin and C peptide
27
Insulin receptors are...
Tyrosine kinase --> PIP3 and RAS/MAP
28
PIP3 pathway in response to insulin results in
GLUT4 vesicles translocated to membrane and glycogen, lipid and protein synthesis
29
RAS/MAP pathway leads to
Cell growth, DNA synthesis
30
Effects of insulin
```
Anabolic --
Increased glc transport in skeletal m/adipose tissue
Increased glycogen synth/storage
Increased trig synthesis
Increased Na retention (kidneys)
Increased protein synth (mms)
Increased cellular uptake of K and amino acids
Less glucagon release
Less lipolysis in adipose tissue
```
31
Does insulin cross placenta?
No
32
Insulin dependent glucose transporters and location
GLUT4 -- adipose tissue, striated muscle (increased by exercist)
33
Insulin independent glucose transporters and location
GLUT1: RBCS, brain, cornea, placenta
GLUT2 (bidirectional): B islet cells, liver, kidney, SI
GLUT3: brain, placenta
GLUT5 (fructose): spermatocytes, GI tract
Insulin independent glucose uptake in BRICK L
Brain, RBCs, Intestine, Cornea, Kidney, LIver
34
Insulin release related to sympathetic stimulation
Decreased by alpha2
| Increased by beta2
35
Process of excreting insulin in response to glucose
Glucose enters B cells --> more ATP made from metabolism of glc --> closes K channels (target of SUs) --> depolarization --> voltage gated Ca channels open --> Ca influx --> insulin exocytosis
36
Glucagon function
Glycogenolysis, gluconeogenesis, lipolysis, ketone prodxn -- secreted in response to hypoglycemia, inhib by insulin, hyperglycemia, somatostatin
37
CRH -->
Increases ACTH, MSH, B-endorphin, lower in chronic exogenous steroid use
38
Dopamine-->
Less PRL, TSH (dopamine antagonists --> galactorrhea due to hyper prolactinemia
39
GHRH-->
Increased GH
40
Tesamorelin
GH analog used to tx HIV assc lipodystrophy
41
GnRH-->
Incereased FSH, LH --> suppressed by hyperprolactinemia
Tonic GnRH-->suppresion of HPG axis
Pulsatile GnRH -->puberty, fertility
42
PRL--->
Less GnRH
43
Pituitary prolactinoma-->
Amenorrhea, osteoporosis, hypogonadism, galactorrhea via suppression of GnRH
44
Somatostatin-->
Decreases GH, TSH --> analogs can treat acromegaly (octreotide)
45
TRH-->
Increased TSH, PRL; increased TRH in 1o/2o hypothyroidism (trying to compensate) may increase prolactin secretion --> galactorrhea
46
PRL fxn-->
Stimulates milk prodxn in breast, inhib ovulation in females/spermatogenesis in males by inhib of GnRH synth/release (increase assc w/ decreased libido)
47
Dopamine and PRL
Dopamine inhibits PRL secretion via tuberoinfundibular pathway of hypothalamus
48
Dopamine agonists
Bromocriptine --> inhib PRL secretion --> tx of prolactinoma
49
Dopamine antagonists and estrogens-->
stimulate PRL secretion
50
GH aka
Somatotropin
51
Fxn of GH
Stimulates linear growth/muscle mass via action of IGF-1 from liver, increases insulin resistance (diabetogenic)
52
IGF-1 aka
Somatomedin C
53
GH regulation
GHRH --> pulsatile release of GH esp during exercise, deep sleep, puberty, hypoglycemia
Inhibition of secretion by glc, somatostatin (negative feedback on somatomedin)
54
Excess GH
Gigantism in children, acromegaly in adults -- tx w/ stomatostatin analogs (octreotide) or surgery
55
Ghrelin-->
Hunger stimulation (orexigenic) and GH release
56
Ghrelin produced by
Stomach
57
Ghrelin increased by
Sleep deprivation or Prader Willi
58
Leptin-->
Satiety
59
Leptin made by
Adipose tissue
60
Leptin mutations-->
Congenital obesity
61
Leptin reduced by
Sleep deprivation, starvation
62
Endocannabinoids
Act at cannabinoid receptors in hypothalamus and nuc accumbens --> homeostatic/hedonic control of food intake --> increased apptite
63
ADH synthesis
Hypothalamus (supraoptic nuclei)
64
ADH fxn
Regulates serum osmo via V2 and BP via V1
| Decreases serum osmo, increases urine osmo
65
How ADH works
Regulates aquaporin channel insertion in principle cells of collecting duct
66
When is ADH lower?
Central DI (can be normal or high in nephrogenic DI)
67
Cause of nephrogenic DI
Mutatio in V2
68
Desmopressin acetate
ADH analog -- tx of central DI and nocturnal enuresis
69
Regulation of ADH
Osmoreceptors in thalamus, hypovolemia
70
17alpha hydroxylase def -- effect on mineralocorticoids, cortisol, sex hormones, BP, K+, assc labs, presentation
```
Mineralocorticoids: increased
Cortisol: decreased
Sex hormones: decreased
BP: increased
K+: decreased
Labs: low androstendione
Presentation:
XY-->ambiguous, undescended testes
XX-->lacks 2o sexual development
```
71
21 hydroxylase def -- effect on mineralocorticoids, cortisol, sex hormones, BP, K+, assc labs, presentation
```
Most common
Mineralocorticoids: Decreased
Cortisol: Decreased
Sex hormones: increased
BP: low
K+: High
Labs: High renin, high 17-hydroxy progesterone
Presentation: Salt wasting in infancy, precocious puberty in childhood, XX: virilization
```
72
11 B hydroxylase def -- effect on mineralocorticoids, cortisol, sex hormones, BP, K+, assc labs, presentation
```
Mineralocorticoids: Decreased aldo, but high 11-deoxycorticosteron (-->increase in BP)
Cortisol: Decreased
Sex hormones: Increased
BP: Increased
K+: Low
Labs: Low renin activity
Presentation: XX: virlization
```
73
Common features of multipl CAH
Enlargement of adrenal (increased ACTH), skin hyperpigmentation
74
Cortisol binds to
Cortisol binding globulin
75
Cortisol fxns
Increased appetite
Increase BP
- Upreg of alpha 1 on arterioles --> increased sens to NE/Epi
-High conc. binds to mineralocorticoid (aldo) receptors
Increase insulin resistance
Increase gluconeogenesis, lipolysis, proteolysis (less glc utilization)
Decrease fibroblast activity (-->poor wound healing, decreased collagen synth, increase in striae)
Decreased inflam/immuni response
- Inhib prdxn of leukotriences/PGs
- Inhib WBC adhesion (-->neutrophilia)
- Blocks histamine release from mast cells
- Eosinopenia, lymphopenia
- Blocks IL-2 prodxn
Less bone formation (decreases activity of osteoblasts)
A BIG/FIB
76
Regulation of cortisol
CRH-->ACTH-->cortisol prodxn --> excess downregs CRH, ACTH, and cortisol
BUT chronic stress -->prolonged secretion of cortisol
77
Calcium in plasma forms
Ionized/free>albumin>anions
78
Calcium in plasma change in binding...
Increased pH --> more affinity of albumin for Ca (increased neg charge) --> binding of Ca --> hypocalcemia (cramps, pain, paresthesias, carpopedal spasm)
79
Regulation of PTH
Ionized/free Ca
80
Vit D action
Increased absorption of dietary Ca and PO4, enhances bone mineralization
81
Vit D reg
Increased by PTH, low Ca and low PO4
82
Deficiency of vit D
Ricket in kids
Osteomalacia in adults
Due to malabsorption, low sunlight, poor diet, CKD
83
24 hydroxylase and Vit D
Makes 24,25 OH2 D3 -- inactive
84
PTH action
Increased Ca/PO4 reabsorption from bone
Increased kidney reabsorption of Ca in DCT
Decreased reabsorption of PO4 in PCT
Increased dihydroxy vit D by stim of kidney 1alpha hydroxylase in prox tubule
NET LOSS OF serum PO4, increase in urine cAMP, increase in serum Ca
85
PTH secreted by
Chief cells of parathyroid
86
PTH action on bone --
Stimulates RANKL on osteoblasts/osteocytes
| --> binds RANK on osteoclasts to stimulate them to resorb bone
87
Intermitten PTH release -->
Bone formation
88
Malignancies of PTHrP
SCC of lung, RCC
89
Regulation of PTH
Secretion sim: low Ca, high PO4, low Mg
| Secretion inhib: REALLY low Mg
90
Causes of low Mg
Diarrhea, aminoglycosides, diuretics, EtOH abuse
91
What cells secrete calcitonin?
Parafollicular of thyroid
92
Action of calcitonin
Decreases bone resorption of Ca (stim by increased Ca); not really significant in normal Ca homeostasis
93
Thyroid hormone is produced in
Follicles of thyroid (t3 conversion in tissues mostly)
94
Fxn of thyroid hormones
Bone growth (GH synergism)
CNS maturation
Increases B1 receptors in heart (Increases CO, HR, SV, contractility)
Increased BMR by increase of Na/K ATPase activity -->more O2 consumption, RR, body temp
Increase in glycogenolysis, gluconeogenesis, lipolysis
(4 B's -- brain mat, bone growth, beta adrenergic, BMR)
95
Reg of thyroid hormone
TRH from hypothalamus-->TSH from ant pituitary-->stimulation of follicular cells (also via TSI in graves)
Negative feedback of T3/T4 on hypothalamus and ant pituitary
96
Wolff Chaikoff effect
Excess iodine --> temporary inhib of TPO --> less iodine organification --> less T3/4 prodxn
97
Thyroid hormone synthesis
Iodine/Na transporter into thyroid foll cell-->goes into colloid-->I gets oxidized to I2 via TPO --> organification of I2+TG by TPO resulting in --> MITs and DITs --> TPO causes coupling so some DIT/MITs combine to make T3/T4 (still attached to TG) --> endocytosed back into follicular cell--> proteases cleave thryoid hormones from TG (gets recycled) --> released into circ (5' deiodinase catalyzes T4-->T3 in tissues
98
Cases of low TBG
Hepatic failure, steroids
99
Cases of high TBG
Pregnancy, OCP (increased by estrogen!)
100
Action of glucocorticoids on thyroid hormones
Inhibition of peripheral T4-->T3
101
cAMP signalling pathway hormones
FSH, LH, ACTH, TSH, CRH, h-CG, ADH (V2), MSH, PTH, calcitonin, GHRH, glucagon, histamine (H2)
FLAT ChAMP +calcitonin, GHRH, glucagon, histmine
102
cGMP signalling pathway hormones
BNP, ANP, EDRF (NO)
BAD GraMPa (vasodilators)
103
IP3 signalling pathway hormones
GnRH, Oxytocin, ADH (V1), TRH, Histamine (H1), Ang II, Gastrin
GOAT HAG
104
Intracellular receptor hormones
Prog, E2, Testosterone, Cortisol, Aldosterone, T3/T4, Vit D
PET CAT on TV
105
Receptor TK homones
Insulin, IGF-1, FGF, PDGF, EGF (MapK pathway, growth factors)
106
Nonreceptor TK hormones
Prolactin, Immunomodulators (cytokines, IL2, IL6, IFN), GH, G-CSF, EPO, TPO
(Jak-STAT, acidophils and cytokines)
PIGGlET
107
Effect of SHBG in men
Increased --> more bound Test --> lowers free T --> gynecomastia
108
Effect of SHBG in women
Low --> more free T --> hirsuitism
109
Effect of OCPs/pregnancy on SHBG-->
Increases it
110
Causes of Cushing syndrome
Increased cortisol:
- Exogenous corticosteroids
- 1o adrenal adenoma, hyperplasia, carcinoma
- ACTH secreting pituitary adenoma and paraneoplastic ACTH secretion
111
Exogenous corticosteroids labs
Low ACTH, bilat adrenal atrophy -- most common cause
112
1o adrenal adenoma, hyperplasia, carcinoma labs
Low ACTH, atrophy of uninvolved gland, can present w/ pseudohyperaldosteroneism via stim of aldor
113
ACTH secreting pituitary adenoma and paraneoplastic ACTH secretion labs
High ACTH, bilat adrenal hyperplasia
114
Majority of endogenous ACTH cushings syndrome
Cushings disease (ACTH pituitary adenoma)
115
Findings in cushings syndrome
HTN, wt gain, moon facies, abdominal striae, truncal obesity, buffalo hump, skin changes (thinning, striae), osteoporosis, hyperglycemia (due to ins resistance), amenorrhea, immunosuppression
116
Screening algorithm for Cushings
1. ACTH measured via 24 hr free urine, late night salivary, inadequate suppression via 1 mg dexamethasone
IF SUPPRESSED -- ACTH indepented like exogenous or adrenal tumor
IF ELEVATED -- ACTH dependent
2. Do CRH stimulation test or 3. High dose dex
Ectopic secretion -- CRH doesn't affect ACTH and no suppression w/ high dose dex (do CT of chest/abdomen/pelvis)
Pituitary adenoma -- CRH will increase ACTH and cortisol, high dose dex will suppress (MRI of pituitary)
117
Adrenal insufficiency sx
Weakness, fatigue, orthostatic hypotension, muscle aches, wt loss, GI disturbances, sugar/salt cravings
118
Tx of adrenal insufficiency
Supplement glucocorticoids/mineralocorticoids
119
Diagnosis of adrenal insufficiency
Measure serum lytes, cortisol, ACTH; metyrapone stim -- blocks last step of cortisol synth (11-deoxycort-->cort)
120
Diagnosis results in 1o adrenal insufficiency
Low cort, high ACTH, metyrapone --> increased ACTH but low 11-deoxycortisol
121
Diagnosis results in 2o/3o adrenal insufficiency
Low cort, low ACTH, metyrapone --> low ACTH and 11 deoxycortisol
122
1o adrenal insufficiency
Def of aldo and cortisol due to loss of gland fxn --> hypotension (hyponatremic volume contraction), hyperkalemia, metabolic acidosis, skin/mucosal hyperpigmentation (increased MSH from ACTH prodxn)
123
Acute 1o adrenal insufficency
Suden onset (e.g. massive hemorrhage) --> shock
124
Chronic 1o adrenal insufficiency aka
Addison disease
125
Chronic 1o adrenal insuff due to
Adrenal atrophy/destruction by diease (autoimmune in west, TB in developing world)
126
Associated with 1o adrenal insuff
Autoimmune polyglandular syndromes
127
Waterhouse-Friedrichsen syndrome
Acute adrenal insuff due to adrenal hemorrhage assoc w septicemia (N. gonorrhea), DIC, endotoxic shock
128
2o adrenal insuff
Decreased pituitary ACTH prodxn -- no skin pigmentation, no hyperkalemia (aldo is fine bc of intact RAAS)
129
3o adrenal insuff
Chronic exogenous steroid use -- precipitated by abrupt w/drawal (No effect on aldo synth)
130
Hyperaldosteronism --
Increased aldo --> HTN, decrease/normal K
131
1o hyperaldosteronism
Adrenal adenoma (Conn syndrome) or bilateral adrenal hyperplasia --> high aldo and low renin
132
2o hyper aldo seen in...
Pt w/ renovascular HTN, JG cell tumors that make renin, edema
133
Neuroendocrine tumors
Originate from Kulchitsky and enterochromaffin like cells -- thyroid medullary carcinoma, lung small call carcinoma, islet cell tumor of pancreas, pheochromocytoma
134
Neuroendocrine tumors contain and secrete
Contain -- APUD
| Secrete: 5HIAAA, NSE, chromogranin A
135
Neuroblastoma demographics..
Most common adrenal medulla tumor in children under 4
136
Origin of neuroblastoma
Neural crest
137
Neuroblastoma location
Anywhere in sympathetic chain
138
Presentation of neuroblastoma
Abdominal distension, firm/irregular mass (can cross midline unlike Wilms), opsoclonus-myoclonus syndrome (dancing eyes, dancing feet)
139
Lab tests in neuroblastoma
Increased HVA and VMA in urine
140
Histology of neuroblastoma
Homer Wright rosettes (also in medulloblastoma), NSE and Bombesin +
141
Genetics of neuroblastoma
Overexpression of N-myc
142
Classification of neuroblastoma
APUD tumor
143
Pheochromocytoma demographics
Most common tumor of adrenal medulla in adults
144
Derivation of pheochromocytoma
Chromaffin cells (from neural crest)
145
Germline mutations associated w/ pheochromocytoma
NF1, VHL, RET (MEN2A/B)
146
Rule of 10s
```
In pheochromocytoma
10% malignant
10% bilat
10% extra adrenal (bladder wall, organ of Zuckerkandl)
10% calcify
10% kids
```
147
Sx of pheochromocytoma
Due to secretion of Epi. NE, and Dop --> episodic HTN, headache, perspiration, palpitations, pallor in spells (relapse/remit)
148
Labs in pheochromocytoma
Increased catecholamines and metanephrines in urine/plasma
149
Tx of pheochromocytoma
Irreversible alpha ant -- prevent hypertensive crisis (phenoxybenzamine) followed by B blockers and then resection
150
Hair in hypothyroid
Coarse brittle
151
Hair in hyperthroid
Fine
152
Myopathy in hyper vs hypothyroid
Both proximal, but hypothyroid can have low CK and hyper has NL CK
153
Causes of smooth/diffuse goiter
Graves, Hashimoto, Iodine def, TSH secreting pit adenoma
154
Causes of nodular goiter
Toxic multinodular goiter
Thyroid adenoma
Thyroid cancer
Thyroid cyst
155
Cholesterol in hypo vs hyperthyroid
Hypercholesterolemia (decreased LDLr expression) in hypo
| Hypocholesterolemia (increased LDLr expression) in hyper
156
Myxedema in hypo vs hyperthyroid
Hypo -- facial/periorbital
| Hyper -- pretibial
157
Hashimoto thyroiditis abs
Anti TPO or anti TG
158
Clinical course of hashimotos
Early hyperthyroid (follicular rupture) --> hypothyroid
159
Histology of hashimotos
Hurthle cell change, lymphoid aggregates w/ germinal centers
160
Hashimoto presentation
Moderately enlarged nontender thyroid
161
Congenital hypothryoidism causes
Maternal hypothyroid, thyroid agenesis, iodine def, dyshormonogenetic goiter
162
Congenital hypothyroidism findings
Pot bellied, Pale, Puffy faces w/ Protruding umbilicus, Protuberant tongue, Poor brain dev (6Ps)
163
Subacute granulomaous thyroiditis (de Quervain) clinical course
Self limited after flu like illness (e.g. viral infxn) hyperthyroid-->hypothyroid
164
Histology of de Quervain thyroiditis
Granulomatous inflam
165
Findings in de Quervain thyroiditis
Increased ESR, jaw pain, TENDER thyroid
166
Subacute lymphocytic thyroiditis
Autoimmune rxn in young/middle aged women post partum -- mild enlargement of thyroid w/ patchy destruction of follicles; transient mild thyrotoxicosis-->hypothyroid
PAINLESS
167
Riedel thyroiditis
Thyroid replaced by fibrous tissue w/ inflamm inflitrate, can extend to local structures (trachea/esophagus); 1/3 are hypothyroiid
Assc w/ IgG4 systemic disease (autoimmune pancreatitis, retroperitoneal fibrosis, noninfectionaortitis)
Fixed, hard, painless goiter
168
Graves disease abs
TSI -- stimulates TSHr on thyroid and dermal fibroblasts (-->pretibial myxedema)
169
Pathophys of exopthalmos
T cell infiltration of retroorbital space by activated T cells --> increased cytokines (TNFalpha, IFN gamma) --> fibroblasts secrete GAGs -->osmotic muscle swelling, finlamm, increased adiopocytes --> exopthalmos
170
Graves HLA associations
HLA DR3, HLA B8
171
Toxic multinodular goiter
Patches of hyperfunctioning follicular cells distended w/ colloid working independent of TSH (usually TSHr mutation) --> more T3 T4 released
172
Thyroid storm
Untreated/undertreated hyperthyroidism + stress (infxn, trauma, etc) --> agitation, fever, delirium, fever, diarrhea, coma, tachyarrhythmia (can cause death)
173
Thyroid storm tx
```
B blockers (Propanolol), PTU, corticosteroids (Prednisone), Potassium iodide (Lugol idoine)
(4Ps)
```
174
Jod-Basedow phenomenon
Thyrotoxicosis if pt w/ iodine def and partiallly autonomous thyroid tissue is made iodine replete (opp of Wolff Chaikoff)
175
Thyroid adenoma
Benign solitary growth of thyroid, usually cold
| Rarely can cause hyperthyroidism
176
Thyroid adenoma histology
Follicular usually -- no capsular/vascular invasion (see in follicular carcinoma)
177
Thyroid cancer diagnosis
Fine needle aspiration, tx is thyroidectomy
178
Thyroidectomy complications
Hoarseness (recurrent laryngeal n. injury), hypocalcemia (parathyroid removal), transection of recurrent/sup laryngeal n during ligation of inf thyroid a. and sup thyroid a. respectively
179
Papillary carcinoma incidence, prognosis
Most common, good prognosis
180
Papillary carcinoma histology
Empty-appearing nuc w/ central clearing (oprhan annie), psammoma bodies, nuclear grooves
181
Papillary carcinoma associations/genetics
RET, BRAF, childhood irradiation
182
Follicular carcinoma prognosis
Good
183
Follicular carcinoma histology
Invades thyroid capsule/vasculature, has uniform follicles
184
Spread of follicular carcinoma
Hematogenous!
185
Genetics of follicular carcinoma
RAS
186
Medullary carcinoma origin cells
Parafollicular C cells
187
Medullary carcinoma makes...
Calcitonin --> amyloid
188
Medullary carcinoma histology
Sheets of cells in amyloid stroma, stains w/ congo red
189
Mutations assoc w/ medullary carcinoma
MEN2A/2B RET
190
Undifferentiated/anaplastic carcinoma demographic
Older patients
191
Undifferentiated/anaplastic carcinoma prognosis
Poor -- invades local structures
192
What disease is lymphoma associated w/?
Hashimoto's
193
1o hypoparathyroidism causes
Surgical, resection, autoimmune, DiGeorge
194
hypoparathyroid findings
Hypocalcemia --> tetany, hyperphosphatemia
195
Chovstek sign
Tapp facial nerve --> facial mm contraction
196
Trousseau sign
Occlusion of brachial a w/ BP cuff --> carpal spasm
197
2o hypoparathyroidism causes
Vit D deficiency, low Ca intake, chronic renal failure
198
1o hyperparathyroidism causes
Hyperplasia, adenoma, carcinoma
199
PTH independent hypercalcemia
Excess Ca intake, cancer, high vit D
200
Pseudohypoparathyroidism 1A aka
Albright hereditary osteodystrophy
201
Pseudohypoparathyroidism 1A pathophys
Defective Gs protein alpha subunit--> Unresponsiveness of kidney to PTH --> hypocalcemia despite high PTH
202
Pseudohypoparathyroidism 1A findings
Short 4/5 digits, short stature
203
Pseudohypoparathyroidism 1A genetics
AD, must be inherited from mother due to imprinting
204
PseudoPSEUDOhypoparathyroidism
Phyical exam features like Albright's but no end-organ PTH resistance --- defect inherited from father
205
1o hyperparathyroidism findings
Hypercalcemia, hypercalciuria (-->kidney stones), polyuria, hypophosphatemia, high PTH, high ALP, high cAMP in urine; usually asymptomatic, but may have weakness/constipation, abdominal/flank pain (kidney stones, acute pancreatitis), depression
206
Osteitis fibrosa cystica
Cystic bone spaces filld w/ brown fibrous tissue made of osteoclasts and hemosiderin from hermorrhages; due to high PTH (esp 1o)
207
2o hyperparathyroidism findings
Hypocalcemia, hyperphosphatemia in chronic renal failure (low in other cases), high ALP, high PTH
208
3o hyperparathyroidism causes
Refractory (autonomous) hyperparathyroidism resulting from chronic renal disease, high Ca, really high PTH
209
Renal osteodystrophy
Renal disease --> 2o/3o hyperparathyroidism --> bone lesions
210
Familial hypocalciuric hypercalcemia
Defective Gcoupled Ca sensing receptors --> higher than normal Ca levels to suppress PTH; excessive renal Ca reuptake --> mild hypercalcemia and hypocalciuria w/ normal/increased PTH levels
211
Nelson syndrome
Enlargement of existing ACTH secreting pituitary adenoma after bilateral adrenalectomy for refractory Cushin disease (removal of cortisol feedback mechanism)
212
Nelson syndrome findings
Hyperpigmentation, headaches, bitemporal hemianopia
213
Tx of Nelson syndrome
Pituitary irradiation or surgical resection
214
Acrogmegaly cause
Usually pituitary adenoma
215
Acromegaly findings
Large tongue w/ deep furrows, deep voice, large hands/feet, coarsening of facial features, frontal bossing, diaphoresis, impaired glc tolerance, increased risk of colorectal polyps/cancer
216
Dianosis of acromegaly
High IGF-1, failure to suppress serum GH following oral glc, pituitary mass on brain MRI
217
Tx of acromegaly
Pituitary adenoma resection, octreotide (somatostatin analog), pegvisomant (GHr antagonist), dopamine agonists (cabergoline)
218
Laron dwarfism pathophysiology
Defective GHr --> less linear growth, high GH, low IGF-1
219
Laron dwarfism clinical features
Short height, small head circumfrence, facies w/ saddle nose and prominent forehead, delayed skeletal maturation, small genitalia
220
Di symptoms
Intense thirst and polyuria, no ability to concentrate urine
221
Central DI causes
Pituitary tumor, autoimmune, trauma, surgery, ischemic encephalopathy, idopathic
222
Findings in central Di
Low ADH, low urine specific grav, high serum osmo (>290), hyperosmotic volume contraction
223
Water deprivation in central DI
>50% increase in urine osmo ONLY AFTER ADH analogue admin
224
Tx of central DI
Desmopressin acetate, hydration
225
Nephrogenic DI etiology
Hereditary (ADHr mutation), 2o to hypercalcemia, hypokalemia, lithium, demeclocycline (ADH ant)
226
Nephrogenic DI findings
Normal or increased ADH, low urine SG, high serum osmo (>290), hyperosmotic volume contraction
227
Water deprivation test in nephrogenic DI
Minimal change in urine osmo even after admi of ADH analog
228
Tx of nephrogenic DI
HCTZ, indomethacin, amiloride, hydration, dietary salt restriction, avoidance of offending agent
229
SIADH findings
Excessive free water retention, euvolemic hyponatremia w/ continued urinary Na excretion, urine osmo>serum osmo
230
SIADH body response
Water retention --> lower aldo and increase ANP?BNP --> increase Na secretion in urine --> normal ECF volume --> euvolemic hyponatremia
231
Result of low serum Na
Cerebral edema, seizures, correction too quickly --> osmotic demyelination syndrome (Central pontine myelinolysis)
232
SIADH causes
Ectopic ADH (small cell lung cancer), CNS disorders/headtrauma, pulmonary disease, drugs (e.g. cyclophosphamidee)
233
Tx of SIDADH
Fluid restriction, salt tablets, IV hypertonic saline, diuretics, conivaptan, tolvaptain, demeclocycline
234
MOA of vaptans
Vasopressin receptor antagonists
235
Ddx between SIADH and psychogenic polydipsia
Increased urine osmo in water deprivation test --> psychogenic polydisia
236
Causes of hypopituitarism
Nonsecreting pituitary adenoma, craniopharyngioma, sheean syndrome, empty sella syndrome, pituitary apoplexy, brain injury, radiation
237
Tx of hypopituitaryism
HRT
238
Sheehan syndrome
Ischemic infarct of pituitary after postpartum bleeding, pregnancy induces growth of pituitary --> more susceptible to hypoperfusion; present w/ failure to lactate, absent menstruation, cold intolerance
239
Empty sella syndrome
Atrophy or compression of pituitary (in sella turcica), obese women, idiopathic
240
Pituitary apoplexy
Sudden hemmorhage of pituitary -- usually in presence of existing pituitary adenoma; presents w/ sudden severe headache, visual impairment (bitemporal hemianopia, diplopia due to CN III palsy), feats of hypopituitarism
241
DKA in..
DM 1
242
Hyperosmolar coma in
DM2
243
Complications of diabetes
Small vessel disease (diffuse thickening of basement membrane) -> retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation), glaucoma, neuropathy, nepropathy (nodular glomerulosclerosis, aka Kimmelstiel Wilson nodules --> progressive proteinuria [initially microalbuminuria, ACE inhibitors are renoprotective] and arteriolosclerosis-->HTN; both lead to chronic renal failure)
Large vessel atherosclerosis, CAD< peripheral vascular occlusive disease, gangren --> limb loss, cerebrovascular disease. MI most common cause of death
Osmotic damage (sorbitol accumulates in organs w/ aldose reductase/absent sorbitol DH) --> nephropathy (motor, sensory [glove and stocking distribution] and autonomic degen as well as cataracts
244
HbA1C DM cutoff
>6.5%
245
Fasting plasma glucose DM cutoff
>126 (fasting >8hrs)
246
2 hour OGTT DM cutoff
>200
247
Abs in type 1 DM
Glutamic acid decarboxylase abs, destroy B cells
248
HLA association in type 1 DM
HLA DR3/4
249
Histology of type 1 DM
Islet leukocytic infiltrate
250
Histology of type 2 DM
Islet amyloid polypeptide (IAPP) deposits
251
Pathophysiology of ketoacidosis
Excess fat breakdown and increased ketogenesis from increased free fatty acids made into ketone bodies
252
Signs/sx of DKA
Delirium/psychosis, Kussmaul respirations, Abdominal pain/nausea/vom, dehydration, fruity breath odor
253
Labs in DKA
Hyperglycemia, high H+, low HCO3 (anion gap met acidosis), high blood ketones, leukocytosis, hyperkalemia (but depleted intracell K due to transcellular shift from low insulin and acidosis -- so total body K is actually depleted)
254
Complications of DKA
Life threatening mucormycosis (by Rhizopus), cerebral edema, cardiac arrhythmias, heart failure
255
Tx of DKA
IV fluids, IV insulin, K+ to replete IC stores, glucose to prevent hypoglycemia if necessary
256
Hyperosmolar hyperglycemic state
Profound hyperglycemia and dehydration --> increased serum osmo --> elderly T2D w/ limited ability to drink
Hyperglycemia -_> excesive osmotic diuresis -->dehydration -->eventually onset of HHNS
257
Sx of hyperosmolar hyperglycemic state
Thirst, polyuria, lethargy, focal neuro deficits (seizures), can progress to coma and death
258
Labs in HHGS
Hyperglycemia (like >600), high serum osmo (>320), no acidosis
259
Tx of HHGS
Aggressive IV fluids, insulin
260
Glucagonoma
Tumor of pancreatic alpha cells -->make glucagon --> dermatitis (necrolytic migratory erythema), diabetes (hyperglycemia), DVT, declining weight, depression
261
Tx of glucagonoma
Ocretotide, surgery
262
Insulinoma
Tumor o B cells --> make too much insulin --> hypoglycemia
| Will have low glc but high C peptide, ~10% cases assc w/ MEN 1, tx by resection
263
Whipple triad
Low blood glucose, symptoms of hypoglycemia (lethargy, syncope, diplopia), and resolution of symptoms after normalization of glucose lvls (in insulinoma)
264
Somatostatinoma
Tumor of delta cells --> too much somatostatin --> less secretion of secretin, CCK, glucagon, insulin, gastrin, GIP
Present w/ diabetes/glc intolerance, steatorrhea, gallstones, achlorhydria
265
Tx of somatostatinoma
Surgical resect, octreotide
266
Carcinoid syndrome caused by
Carcinoid tumores from neuroendocrine cells
267
Property of neuroendocrine tumors by histology
Rosettes
268
Cause a lot of carcinoid syndrome
Metastatic small bowel tumors (secrete high serotonin)
269
Sx of carcinoid syndrome
Recurrent diarrhea, cutaneous flushing, asthmatic wheezing, right sided valvular heart disease (tricuspid regurg, pulmonic stenosis
270
Labs in carcinoid syndrome
High 5HIAA in urine, niacin def
271
Tx of carcinoid syndrome
Surgical resection, somatostatin analog (octreotide)
272
Rule of 1/3s
1/3 of carcinoid tumors metastasize, 1/3 present w/ 2nd malignancy, 1/3 are multiple
273
Most common malignancy in SI
Carcinoid tumor
274
Z-E syndrome
Gastrin secreting tumor (gastrinoma) of pancreas or duodenum --> acid hyper secretion --> recurrent ulcers in duodenum and JEJUNUM
Presentation: abdominal pain (PUD, distal ulcers)< diarrhea (malabsorption)
275
Z-E Syndrome test
Positive secretin stim test -- gastrin levels elevated after admin of secretin which normally inhibs gastrin
276
Z-E association
MEN1
277
MEN syndrome inheritance
AD
278
MEN 1 disease
```
Pituitary tumors (prolactin or GH)
Pancreatic tumors (Z-E, insulinomas, VIPomas, glucagonomas)
parathyroid adenomas
```
279
MEN 1 genetics
Menin mutation -- tumor suppressor on chr 11
280
MEN 2A disease
Parathyroid hyperplasia
Medullary thyroid carcinoma (C cells -- req prophylactic thyroidectomy)
Pheochromocytoma
281
MEN 2A genetics
RET in cells of neural crest origin
282
MEN 2B disease
Medullary thyroid carcinoma
Pheochromocytoma
Mucosal neuromas (oral/intestinal ganglioneuromatosis)
Marfanoid habitus
283
MEN 2B genetics
RET mutation
