Endocrinology Flashcards
1
Q
Most common ectopic thyroid tissue site
A
tongue (lingual thyroid). removal may result in hypothyroidism if it is the only thyroid tissue present.
2
Q
branchial cleft cyst origin
A
persistent cervical sinus
3
Q
Thyroid tissue origin
A
endoderm
4
Q
parafollicular cell origin
A
neural crest
5
Q
adrenal cortex and medulla origin
A
cortex from mesoderm, medulla from neural crest
6
Q
chromaffin cell regulatory control
A
preganglionic sympathetic fibers
7
Q
Melanotropin (MSH) origin
A
Intermediate lobe of pituitary.
8
Q
Anterior pituitary other name
A
adenohypophysis
9
Q
Anterior pituitary origin
A
oral ectodrm (Rathke pouch)
10
Q
Hormones that share alpha subunit
A
TSH, LH, FSH, and hCG. Beta subunit determines specificity.
11
Q
proopiomelanocortin (POMC(
A
ACTH and MSH are derivates of proopiomelanocortin (POMC)
12
Q
hormones of anterior pituitary
A
FLAT Pig: FSH, LH, ACTH, TSH, PRL, GH.
13
Q
Basophils
A
B-FLAT: basophils-FSH, LH, ACTH, TSH
14
Q
Acidophils
A
GH, PRL
15
Q
posterior pituitary other name
A
neurohypophysis
16
Q
Origin of ADH and oxytocin
A
supraoptic and paraventricular nuclei
17
Q
ADH and oxytocin transport
A
carrier proteins called neurophysins.
18
Q
posterior pituitary embryo origin
A
neuroectoderm
19
Q
Islets of langerhans
A
collections of alpha, beta, and gamma endocrine cells in the pancreas.
20
Q
Islets of langerhans origins
A
Arise from pancreatic buds.
21
Q
Islets of langerhans organizations
A
alpha cells peripherally, beta cells centrally, delta cells interspersed
22
Q
alpha cells secrete
A
glucagon
23
Q
delta cells secrete
A
somatostatin
24
Q
Insulin synthesis
A
preproinsulin synthesized in RER –> cleavage of “presignal” –> proinsulin (stored in secretory granules) –> cleavage of proinsulin –> exocytosis of insulin and C-peptide equally.
25
C-peptide significance
increased in insulinoma and sulfonylurea use, whereas exogenous insulin lacks C-peptide
26
Insulin receptors
tyrosine kinase
27
insulin MOA
activates gene transcription
28
anabolic effects of insulin
1) Increases glucose transport in skeletal muscle and adipose tissue.
2) increases glycogen synthesis and storage
3) increases TG synthesis
4) increases Na+ retention
5) increases protein synthesis
6) increases cellular uptake of K+ and amino acids
7) decreases glucagon release
8) decreases lipolysis in adipose tissue
29
insulin and placenta
doesn't cross it, unlike glucose
30
GLUT-4 expression
adipose tissue + striated muscle. exercise can also increase GLUT-4 expression
31
GLUT-1
RBCs, brain, cornea, placenta
32
GLUT-2
beta-islet cells, liver, kidney, small intestine
33
GLUT-3
brain, placenta
34
GLUT-5
fructose, spermatocytes, GI tract
35
insulin-independent glucose uptake pneumonic
BRICK L, brain, RBCs, intestine, cornea, kidney, liver
36
Major regulator of insulin release
glucose
37
Why is there increased insulin sensitivity with oral vs. IV glucose?
Incretins such as glucagon-like peptide 1 (GLP-1), which are released after meals + increased beta cell sensitivity to glucose.
38
Insulin growth pathway
insulin binds to receptor --> tyrosine phosphorylation --> RAS/MAP kinase pathway --> cell growth, DNA synthesis
39
Insulin glucose uptake pathway
insulin binds to receptor --> tyrosine phosphorylation --> Phosphoinositide-3 kianse pathway --> vesicles containing GLUT-4 translocate to membrane --> glucose enters via GLUT-4 carriers
40
Insulin release pathway
Glucose enters beta cells through GLUT-2 transporters --> undergoes glycolysis --> increased ATP/ADP ratio--> ATP-sensitive K+ channels close --> membrane depolarized --> voltage-gated Ca2+ channels open --> Ca2+ influx --> exocytosis of insulin vesicles.
41
glucagon effects
1) glycogenolysis, gluconeogenesis
| 2) lipolysis, ketone production
42
glucagon inhibitors
insulin
hyperglycemia
*somatostain
43
CRH function
increases ACTH, MSH, beta-endorphin
44
CRH and steroids
chronic exogenous steroids decrease CRH
45
dopamine effects
decrease prolactin, decrease TSH
46
tesamorelin
GHRH analog used to treat HIV-associated lipodystrophy
47
prolactin endocrine effects
decreases GnRH (which explains amenorrhea/hypogonadism in pituitary prolactinoma)
48
somatostatin endocrine efects
decreases GH, TSH
49
TRH affects
increases TSH + *prolactin
50
prolactin structure
homologous to GH
51
Prolactin regulation
1) tonically inhibited by dopamine from hypothalamus. 2) Prolactin in turn inhibits its own secretion by increasing dopamine synthesis and secretion from hypothalamus. 3) TRH increases prolactin secretion.
4) renal failure increases prolactin release via reduced prolactin elimination
5) pregnancy --> estrogen --> increased prolactin
52
TRH and hypothyroidism and amenorrhea
TRH increases prolactin secretion in hypothyroidism --> hyperprolactinemia inhibits GnRH
53
cry of baby and prolactine mechanism
cry of baby activates higher cortical centers --> inhibit hypothalamus from secreting dopamine
54
somatotropin
GH
55
somatomedin C
IGF-1
56
GH actions
1) stimulates linear growth and muscle mass through IGF-1 secretion
2) increased insulin resistance
57
GH regulation and secretion
- released in pulses in response to GHRH.
- secretion increases during exercise, deep sleep, puberty, hypoglycemia.
- secretion inhibited by glucose and somatostatin release via negative feedback by somatomedin.
58
orexigenic
means stimulates hunger
59
positive ghrelin regulation
sleep deprivation + Prader-Willi
60
Ghrelin effects
stimulates hunger + GH release
61
leptin source
adipose tissue
62
endocannabinoids and munchies mechanism
act at cannabinoid receptors in hypothalamus and nucleus accumbens, two key brain areas for the homeostatic and hedonic control of food intake, thus increasing appetite.
63
source of ADH
supraoptic nuclei
64
V1 vs. V2 ADH receptors
V2 regulate serum osmolarity, V1 regulate BP
65
ADH level in Central and nephrogenic DI
down in central, normal or increased in nephrogenic
66
nephrogenic DI etiology
mutation in V2 receptor
67
desmopressin acetate 1) MOA, 2) clinical use
ADH analog
| central DI + nocturnal enuresis
68
ADH regulation
osmoreceptors in hypothalamus; hypovolemia
69
17alpha-hydroxylase lab profile
1) mineralocorticoids
2) cortisol
3) sex hormones
4) BP
5) potassium
6) other
1) increased
2) decreased
3) decreased
4) increased
5) decreased
6) decreased andostenedione
70
21-hydroxylase lab profile
1) mineralocorticoids
2) cortisol
3) sex hormones
4) BP
5) potassium
6) other
1) down
2) down
3) up
4) down
5) up
6) increased renin activity + increased 17-hydroxy-progesterone
71
11beta-hydroxylase lab profile
1) mineralocorticoids
2) cortisol
3) sex hormones
4) BP
5) potassium
6) other
1) decreased aldosterone, but increased 11-deoxycorticosterone so increased Bp
2) down
3) up
4) up
5) down
6) decreased renin
72
Cortisol carrier protein
corticosteroid-binding globulin (CBG)
73
cortisol and immunology caveat
exogenous corticosteroids can cause reactivation of TB and candidiasis by blocking IL-2 production
74
cortisol and BP mechanism
1) Upregulates alpha1-receptors on arterioles, increasing sensitivity to NE and E.
2) At high concentrations, can bind to mineralocorticoid (aldosterone) receptors.
75
cortisol actions
BIG FIB.
Increases BP
Increases Insulin resistance
Increases Gluconeogenesis, lipolysis, and proteolysis
Decreases Fibroblast activity (causes striae)
Decreases Inflammatory and Immune responses
Decreases Bone formation (by decreasing osteoblast activity)
76
Cortisol and immune modification mechanism
1) inhibits production of leukotrienes and PGs
2) inhibits WBC adhesions --> neutrophilia
3) blocks histamine release from mast cells.
4) reduces eosinophils
5) blocks IL-2 production
77
cortisol regulation
CRH --> ACTH --> cortisol production. Excess cortisol deceases CRh, ACTH, etc.
78
Plasma calcium forms
1) ionized (45%)
2) bound to albumin (40%)
3) bound to anions (15%)
79
calcium and pH mechanism
increased pH increases affinity (negative charge) of albumin for Ca --> hypocalcemia (cramps, pain, paresthesias, carpopedal spasm).
80
D3 sources
sun, fish, plants
81
D2 sources
Ingestion of plants, fungi, yeasts
82
Vitamin D negative regulation
1,25-(OH)2 feedback inhibits its own production
83
PTH and urine cAMP
PTH increases urine cAMP
84
RANK-L
- receptor activator of NH-kB ligand.
- secreted by osteoblasts and osteocytes.
- Binds RANK (receptor) on osteoclasts and their precursors to stimulate osteoclasts and increase calcium, leading to bone resportion.
85
other regulator of PTH
decreased serum Mg increases PTH, but severely decreased Mg decreases PTH secretion.
86
Common causes of hypomagnesemia
diarrhea, aminoglycosides, diuretics, alcohol abuse.
87
PTH and vitamin D mechanism
positive regulator of 1alpha-hydroxylase
88
calcitonin source
parafollicular cells (C cells) of thyroid
89
Source of T3/T4
Follicles of thyroid. Most T3 formed in target tissues.
90
T3 functions
4 B's --> Brain maturation, Bone growth (synergistic with GH), Beta-adrenergic affects (increases beta1 receptor expression in heart), increases Basal metabolic rate.
*also increases glycogenolysis, gluconeogenesis, lipolysis.
91
How does T3 increase basal metabolic rate?
via increased Na+/K+-ATPase activity, leading to increased O2 consumption, RR, body temperature
92
TSI
thyroid-stimulating immunoglobulin. Graves disease.
93
Wolff-Chaikoff effect
Excess iodine temporarily inhibits thyroid peroxidase, leading to decreased iodine organification, and decreased T3/T4 production.
94
When is TBG (thyroxine-binding globuline) increased and decreased?
Decreased --> hepatic failure, steroids.
| Increased --> pregnancy (via estrogen), OCP use.
95
what converts T4 to T3?
5'-deiodinase
96
T3 vs. T4 potency
T3 binds nuclear receptor with greater affinity
97
Thyroid peroxidase functions
1) oxidation and organification of iodide
| 2) coupling of monoiodotyrosine (MIT) and di-iodotyrosine (DIT).
98
T4 structure
DIT + DIT
99
T3 structure
DIT + MIT
100
propylthiouracil and methimazole and thyroxine actions
Propylthiouracil inhibits both thyroid peroxidase and 5'deiodinase. Methimazole inhibits thyroid peroxidase only.
101
T3/T4 synthesis
Thyroglobulin secreted into follicular lumen --> organification of I2 by thyroid peroxidase --> T4 endocytoses back into epithelial cell --> coupling reaction, T4, T3 to circulation
102
thyroglobulin derived from
tyrosine
103
Iodine uptake mechanism
cotransport with Na
104
hormones that act through cAMP pathway
FLAT ChAMP --> FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2), MSH, PTH.
ALSO --> calcitonin, GHRH, glucagon.
105
hormones that act through cGMP
Think vasodilators. BNP, ANP, EDRF (NO)
106
other name for NO
EDRF, endothelium-derived relaxation factor.
107
Hormones that act through IP3 pathway
GOAT HAG.
| GnRH, Oxytocin, ADH (V1), TRH, Histamine (H1-receptor), Angiotensin II, Gastrin
108
hormones that act through an intracellular receptor
Progesterone, estrogen, testosterone, cortisol, aldosterone, T3/T4, vitamin D
109
hormones that act through receptor tyrosine kinase (MAP kinase pathway)
Insulin, IGF-1, FGF, PDGF, EGF
110
hormones that act through nonreceptor tyrosine kinase (JAK/STAT)
Prolactin, immunomodulators (eg, IL-2, IL-6, IFN), GH, G-CSF, Epo, thrombopoietin.
111
steroid transport
lipophilic. thus must be bound to specific binding globulins to increase their solubility
112
affect of SHBG in men
Sex hormone binding globulin. Lowers free testosterone causing gynecomastia.
113
Cause of hirsutism in women
Decreased SHBG raises free testosterone.
114
SHBG increased with...
OCPs, pregnancy
115
steroid signaling pathway
Hormone binds to receptor in nucleus or cytoplasm --> transformation of receptor to expose DNA-binding domain --> bidns to enhancer-like element in DNA --> activates gene transcription.
116
Most common cause of cushings
exogenous corticosteroids (resulting in decreased ACTH and bilateral adrenal atrophy)
117
Causes of cushings
1) exogenous corticosteroids
2) primary adrenal adenoma, hyperplasia, or carcinoma -- result in decreased ACTH, atrophy of uninvolved adrenal gland. Can also present with pseudohyperaldosteronism.
3) ACTH-secreting pituitary adenoma (Cushing disease).
4) paraneoplastic ACTH secretion
118
what causes most endogenous Cushings?
ACTH-secreting pituitary adenoma.
119
Cushing disease
ACTH-secreting pituitary adenoma
120
Cushing's presentation
HTN, weight gain, moon facies, abdominal striae, truncal obesity, buffalo hump, skin changes, osteoporosis, hyperglycemia (insulin resistance), ammenorrhea, immunosuppression
121
Cushing's screening tests
1) increased free cortisol on 24-hr urinalysis
2) increased midnight salivary cortisol
3) NO suppression with overnight low-dose dexamethasone test.
4) measure serum ACTH
122
What is the use of a high-dose dexamethasone suppression test?
Suppression = Cushing disease
| No suppression = ectopic ACTH secretion
123
What is the use of a CRH stimulation test?
Increased ACTH, cortisol = Cushing disease
| No increased ACTH, cortisol = ectopic ACTH secretion
124
Lab findings for exogenous glucocorticoids or adrenal tumor
ACTH will be LOW
125
Adrenal insufficiency presentation
weakness + fatigue + orthostatic hypotension + muscle aches + weight loss + GI disturbances + sugar and/or salt cravings
126
Adrenal insufficiency diagnosis
1) measurement of serum electrolytes
2) morning/random serum cortisol and ACTH
3) ACTH/cosyntropin stimulation test
4) metyrapone stimulation test
127
difference in labs between primary and 2/3 adrenal insufficiency
low cortisol, high ACTH in primary adrenal insufficiency; low cortisol, low ACTH in secondary/tertiatry due to pituitary, hypothalamic disease
128
metyrapone stimulation test + analyzing results
Metyrapone blocks last step of cortisol synthesis (11-deoxycortisol to cortisol). Normal response is decreased cortisol and compensatory increased ACTH and 11-deoxycortisol. In primary adrenal insufficiency, ACTH is increased but 11-deoxycortisol remains low after test. In secondary/tertiary adrenal insufficiency, both ACTh and 11-deoxycortisol remain decreased after test.
129
primary adrenal insufficiency labs
hypotension (hyponatremic volume contraction) + hyperkalemia + metabolic acidosis.
130
Why do you have skin hyperpigmentation in primary adrenal insufficiency?
Increased MSH, byproduct of ACTH production from proopiomelanocortin (POMC).
131
primary adrenal insufficiency association
Autoimmune polyglandular syndromes.
132
Acute adrenal insufficiency cause and presentation
Massive hemorrhage. Shock.
133
Waterhouse-Friderichsen syndrome
Acute, primary adrenal insufficiency due to adrenal hemorrhage with septicemia (usually neisseria), DIC, endotoxic shock.
134
Addison's causes
autoimmune in Western world, TB in developing.
135
Secondary adrenal insufficiency
Decreased pituitary ACTH production.
136
Difference in presentation with secondary adrenal insufficiency
No skin/mucosal hyperpigmentation, no hyperkalemia (aldosterone synthesis preservd). (secondary spares the skin/mucosa)
137
Cause of tertiary adrenal insufficiency
Chronic exogenous steroid use, precipitated by abrupt withdrawal. Aldosterone synthesis unaffected.
138
Why is there no edema in hyperaldosteronism?
Aldosterone escape.
139
causes of primary hyperaldosteronism
adrenal adenoma (Conn syndrome) or idiopathic adrenal hyerplasia.
140
Causes of secondary hyperaldosteronism
1) renovascular hypertension
| 2) juxtaglomerular cell tumor (due to independent activation of RAAS)
141
secondary hyperaldosteronism labs
Increased aldosterone + increased renin.
142
origin of neuroendocrine tumors
Kulchitsky and enterochromaffin-like cells.
143
examples of neuroendocrine tumors
1) medullary thyroid
2) small cell carcinoma
3) islet cell tumor in pancreas
144
hormones secreted by neuroendocrine tumors
5-HIAA, neuron-specific enolase (NSE), chromogranin A
145
What do neuroendocrine cells contain?
amine precursor uptake decarboxylase (APUD)
146
neuroblastoma origin
neural crest cells
147
Neuroblastoma location
can occur anywhere along the sympathetic chain.
148
Most common presentation of neuroblastoma
Firm, irregular mass that can cross the midline (vs. wilms, which is smooth and unilateral).
149
urine metabolites in neuroblastoma
increased HVA and VMA
150
neuroblastoma tumor markers
Bombesin + NSE positive.
151
neuroblastoma classification
APUD tumor
152
pheochromocytoma genes
Up to 25% associated with germline mutations (NF-1, VHL, RET [MEN 2A, 2B]0
153
pheochromocytoma rule of 10s
10% malignant, bilateral, extra-adrenal, calcify, kids
154
pheochromocytoma management and caveat
Irreversible alpha-antagonists (eg phenoxybenzamine) followed by beta-blockers prior to tumor resection. alpha-blockade must be achieved before giving beta-blockers to avoid a hypertensive crisis.
155
hypothyroid myopathy
proximal muscle weakness, increased CK associated with hypothyroidism
156
hypothyroidism derm presentation
Myxedema (facial/periorbital)
157
appetite in hypo/hyperthyroidism
decreased in hypo, increased in hyper
158
thyrotoxic myopathy
hyperthyroidism -- proximal muscle weakness, normal CK
159
hyperthyroidism derm presentation?
pretibial myxedema (Graves), periorbital edema
160
skin and hair findings in hyperthyroidism
warm, moist skin; fine hair
161
adrenergic response to hyperthyroidism
increased number and sensitivity of beta-adrenergic receptors
162
hyper/hypocholsterolemia in hyper and hypothyroidism
Hypercholesterolemia in hypothyroidism (decreased LDL receptor expression); hypocholesterolemia in hyper (increased LDL receptor expression).
163
Causes of smooth/diffuse goiter
1) Graves disease
2) Hashimoto thyroiditis
3) Iodine deficiency
4) TSH-secreting pituitary adenoma
164
Causes of nodular goiter
1) Toxic multinodular goiter
2) Thyroid adenoma
3) thyroid cancer
4) thyroid cyst
165
antibodies in hashimoto's
```
antithyroid peroxidase (antimicrosomal)
antithyroglobulin
```
166
HLA hashimoto's association
DR5
167
hashimoto and cancer
Increased risk of non-Hodgkin lymphoma (typically of B-cell origin)
168
Hashimoto's caveat
May be hyperthyroid early in course due to thyrotoxicosis during follicular rupture
169
Hashimoto's histology
Hurthle cells, lymphoid aggregates with germinal centers
170
hashimoto's findings
moderately enlarged, NONTENDER thyroid.
171
Causes of cretenisism
1) maternal hypothyroidism
2) thyroid agenesis
3) thyroid dysgenesis
4) iodine deficiency
5) dyshormonogenetic goiter
172
most common cause of cretinism in US
thyroid dysgenesis
173
subacute granulomatous thyroiditis progression
Can be hyper early in course, followed by hypo
174
subacute granulomatous thyroiditis findings
Elevated ESR + jaw pain + *****very tender thyroid.
175
Riedel's etiology
Thyroid replaced by fibrous tissue with inflammatory infiltrate. Fibrosis may extend to local structures (eg, trachea, esophagus), mimicking anaplastic carcinoma.
176
Riedel's caveat
1/3 are hypothyroid
177
Riedel's association
IgG4-related systemic disease (eg, autoimmune pancreatitis, retroperitoneal fibrosis, noninfectious aortitis).
178
Riedel goiter
fixed, hard (rock-like), PAINLESS.
179
other causes of hypothyroidism
1) iodine deficiency
2) goitrogens (amiodarone, lithium)
3) Wolff-Chaikoff effect
180
cause of pretibial myxedema in graves
thyroid-stimulating immunoglobulin stimulates dermal fibroblasts
181
common presentation of graves
during stress (eg, pregnancy)
182
Graves histology
Tall, crowded follicular epithelial cells; scalloped colloid.
183
Exophthalmos in Graves mechanism
Infiltration of retroorbital space by activated T-cells --> increased cytokines (TNF-alpha, IFN-gamma) --> increased fibroblast secretion by hydrophilic GAGs --> increased osmotic muscle swelling, muscle inflammation, and adipocyte count --> exophthalmos.
184
etiology of toxic multinodular goiter
Focal patches of hyperfunctioning follicular cells working independently of TSH usually due to TSH receptor mutations.
185
Hot vs. cold nodules
Hot nodules are rarely malignant.
186
Thyroid storm
uncommon but serious complication that occurs when hyperthyroidism is incompletely treated/untreated and then significantly worsens in the setting of acute stress such as infection, trauma, surgery.
187
thyroid storm presentation
agitation + delirium + fever + diarrhea + coma + tachyarrhythmia (cause of death).
188
thyroid storm labs
can see increased LFts
189
thyroid storm treatment
4 P's: propranolol, propylthiouracial, prednisolone, potassium iodide
190
lugol iodine
potassium iodide
191
Jod-Basedow phenomenon
thyrotoxicosis if a patient with iodine deficiency is made iodine replete. opposite of Wolff-Chaikoff.
192
cold thyroid adenoma
nonfunctional, becomes "hot" or "toxic" via autonomous thyroid hormone production (rare)
193
Most common histology of thyroid adenoma
follicular
194
*Differentiating thyroid adenoma from follicular carcinoma
Absence of capsular or vascular invasion in thyroid adenoma.
195
complication of ligating superior laryngeal artery
transection of superior laryngeal nerve
196
complication of ligating inferior thyroid artery
transection of recurrent laryngeal nerve
197
genetics associated with increased risk of papillary carcinoma
RET + BRAF mutations
198
histology of papillary carcinoma
Empty-appearing nuclei with central clearing (orphan annie eyes), psammoma bodies, nuclear grooves.
199
follicular carcinoma characteristics
Invades thyroid capsule and vasculature (unlike follicular adenoma), uniform follicles; hematogenous spread is common.
200
follicular carcinoma genetics
associated with RAS mutation
201
undifferentiated/anaplastic carcinoma and prognosis
older patients; invades local structures. very poor prognosis.
202
familial hypocalciuric hypercalcemia pathophys
Defective Ca2+-sensing receptor (CaSR) in multiple tissues (eg parathyroids, kidneys). Higher than normal Ca2+ levels required to suppress PTH.
203
familial hypocalciuric hypercalcemia labs
mild hypercalcemia + hypocalciuria + normal to elevated PTH
204
Pseudohypoparathyroidism pathophys
unresponsiveness of kidney to PTH --> hypocalcemia despite elevated PTH levels. Due to defective Gs protein alpha subunit causing end-organ resistance to PTH. Defect must be inherited from mother due to imprinting.
205
Pseudopseudohypoparathyroidism pathophys and presentatoin
physical exam features of Albright hereditary osteodystrophy but without end-organ PTH resistance. Occurs when defective Gs protein alpha-subunit is inherited from father.
206
Laron syndrome
Dwarfism, caused by a mutation in the GH receptor.
207
Labs in Laron syndrome
Increased GH, decreased IGF-1
208
Laron syndrome presentation
Short height + small head circumference + characteristic facies with saddle nose and prominent forehead + delayed skeletal maturation + small genitalia.
209
acromegaly cause
usually pituitary adenoma
210
acromegaly presentation
large tongue with deep furrows + deep voice + large hands and feet + coarsening of facial features with aging + frontal bossing + diaphoresis (excessive sweating) + impaired glucose tolerance (insulin resistance) + increased risk of colorectal polyps and cancer.
211
acromegaly labs
increased IGF-1
212
Nelson syndrome
Enlargement of existing ACTH-secreting pituitary adenoma after bilateral adrenalectomy of refractory Cushing disease (due to removal of cortisol feedback mechanism).
213
Nelson syndrome presentation
Hyperpigmentation+ headaches + bitemporal hemianopia.
214
Nelson syndrome treatment
pituitary irradiation or surgical resection.
215
prolactinoma arises from..
lactotrophs
216
treatment for prolactinoma
dopamine agonists (ergot alkaloids such as bromocriptine, cabergoline), transsphenoidal resection.
217
brown tumor
consists of osteoclasts and deposited hemosiderin from hemorrhages. Causes bone pain.
218
tertiary hyperparathyroidism
refractory (autonomous) hyperparathyroidism resulting from chronic renal disease.
219
tertiary hyperparathyroidism labs
Very hight PTH + hypercalcemia
220
cause of primary hyperparathyroidism
usually parathyroid adenoma or hyperplasia.
221
Primary hyperaparathyroidism labs
hypercalcemia, hypercalciuria, hypophosphatemia, increased PTH, increased ALP, increased cAMP in urine.
222
17,20-lyase
17-hydroxypregnenolone --> dehydroepiandosterone (DHEA
and
17-hydroxyprogesterone --> adrostenedione
223
17alpha-hydroxylase action
Pregnenolone --> 17-hydroxypregnenolone
and
Progesterone - 17-hydroxyprogesterone
224
Aromatase action
Androstenedione --> Estrone
and
Testosterone --> Estradiol
225
How would you differentiate pituitary apoplexy from sheehan's?
apoplexy is hemorrhaging vs. sheehan's, which is ischemic infarct, so you get more of a mass effect presentation with apoplexy.
226
Lab findings in central DI
1) urine SG
2) serum osmolality
3) other
1) Less than 1.006
2) Greater than 290 mOsm/kg
3) Hyperosmotic volume contraction
227
Mechanism of gynecomastia in liver disease
Decreased SHBG
228
Mechanism of hirsutism in PCOS
insulin resistance --> excess insulin lowers SHBG --> increased free testosterone levels.
229
Water deprivation test in central DI vs. nephrogenic DI
Central --> Greater than 50% increase in urine osmolality only after administration of ADH analog.
Nephrogenic --> Minimal change in urine osmolality, even after administration of ADH analog.
230
other causes of nephrogenic DI
Hypercalcemia, hypokalemia, lithium, demeclocycline (ADH antagonist)
231
Lab values in nephrogenic DI
1) urine SG
2) serum osmolality
3) other
1) less than 1.006
2) greater than 290 mOsm/kg
3) hyperosmotic volume contraction
232
nephrogenic DI treatment
HCTZ, indomethacin, amiloride. hydration, avoidance of offending agent.
233
when do you give desmopressin for DI?
1) serum osmolality greater than 295-300
2) hypernatremic
3) urine osmolality doesn't rise despite a rising plasma osmolality.
234
Why is SIADH euvolemic?
Body responds with decreased aldosterone and increased ANP/BNP --> increased urinary sodium secretion --> this normalizes ECF fluid volume.
235
Causes of hypopituitarism
1) pituitary adenoma
2) carniopharyngioma
3) Sheehan
4) Empty sella
5) pituitary apoplexy
6) brain injury
7) radiation
236
sheehan presentation
failure to lactate + absent menstruation + cold intolerance
237
empty sella syndrome and epidimiology
Atrophy or compression of pituitary gland, which lies in the sella turcica. Common in obese women.
238
Other causes of DM
1) unopposed secretion of GH and epinephrine.
| 2) glucocorticoid therapy (steroid diabetes).
239
vascular presentation of DM
arteriolosclerosis, leading to HTN + chronic renal failure. Also large vessel atherosclerosis, CAD, and peripheral vascular occlusive disease.
240
Most common cause of death in diabetes
MI
241
Diabetic neuropathy
motor, sensory (glove and stocking distribution) and autonomic degeneration.
242
Cause of cataracts in DM
sorbitol accumulation in organs with aldose reductase and decreased or absent sorbitol dehydrogenase.
243
DM diagnosis
1) HbA1c greater than 6.5
2) Fasting plasma glucose greater than 126 mg/dL
3) 2-hour oral glucose tolerance test, greater than 200 mg/dL
244
Fasting plasma glucose procedure
Need to fast for at least 8 hours
245
OGTT procedure
Test 2 hours after consumption of 75 g of glucose in water.
246
Why are diabetics thirsty?
hyperglycemia --> increased plasma osmolality --> stimulation of thirst
247
coma/death pathophys in DM
hyperglycemia --> osmotic diuresis --> sodium and potassium wasting --> hypovolemia --> circulation failure and decreased tissue perfusion --> coma/death
248
pathophys of ketogenesis in DM
increased lipolysis --> increased plasma free fatty acids --> ketogenesis, ketonemia, ketonuria --> vomiting.
249
Hyperosmolar hyperglycemia nonketotic syndrome
State of profound hyperglycemia-induced dehydration and increased serum osmolarity, classically seen in elderly type 2 diabetics with limited ability to drink.
250
Hyperosmolar hyperglycemia nonketotic syndrome pathophys
Hyperglycemia --> excessive osmotic diuresis --> dehydration.
251
Hyperosmolar hyperglycemia nonketotic syndrome pathophys
hyperglycemia + increased serum osmolarity + ***no acidosis (ketone production inibited by presence of insulin).
252
Hyperosmolar hyperglycemia nonketotic syndrome treatment
IV fluids, insulin therapy.
253
glucagonoma presentation
dermatitis (necrolytic migratory erythema) + diabetes + DVT + declining weight + depression.
254
glucagonoma treatment
octreotide + surgery
255
Whipple triad
low blood glucose + symptoms of hypoglycemia (lethargy, syncope, diplopia) + resolution of symptoms after normalization of glucose levels.
256
How would you differentiate insulinoma from exogenous insulin use?
Increased C-peptie levels.
257
Insulinoma treatment
surgical resection
258
insulinoma association
10% of cases associated with MEN 1
259
Somatostatinoma labs
Decreased secretion of secretin + CCK + glucagon + insulin + gastrin.
260
Somatostatinoma presenation
diabetes/glucose intolerance + steatorrhea + gallstones
261
Somatostatinoma treatment
surgical resection; octreotide for symptom control
262
carcinoid syndrome rule of 1/3's
1/3 metastasize
1/3 present with 2nd malignancy
1/3 are multiple
263
Most common malignancy in the small intestine
carcinoid
264
Menin and location
tumor suppressor gene on chromosome 11
265
parathyroid presentation of MEN 1 vs. MEN 2A
parathyroid adenomas in MEN 1, parathyroid hyperplasia in MEN 2A
266
Managing type 1 DM
low-carb diet + insulin
267
Managing type 2 DM
dietary modification and exercise for weight loss + oral agents, non-insulin injectables, insulin replacement.
268
Managing gestational DM (GDM)
dietary modifications, exercise, insulin replacement if lifestyle modification fails
269
Rapid acting insulin drugs
Lispro, Aspart, Glulisine (no LAG)
270
Rapid acting insulin drugs SE's
hypoglycemia + lipodystrophy + hypersensitivity reactions
271
Insulin type for DKA
Regular insulin (short acting)
272
Long acting insulins
detemir + glargine
273
biguanides, metformin metabolic actions
Decreased gluconeogenesis
Increased glycolysis
Increased peripheral glucose uptake
274
Metformin contraindication
Renal insufficiency (causes metabolic acidosis)
275
weight loss or gain with biguanides?
modest weight loss
276
1st generation sulfonylureas
clorpropamide, tolbutamide
277
2nd generation sulfonylureas
glimepiride, glipizide, glyburide
278
SE's in first vs. 2nd generation sulfonylureas
1st generation: disulfiram-like effects
| 2nd: hypoglycemia
279
thiazolidinediones clinical use
monotherapy in type 2 DM or combined with other agents.
280
meglitinides
nateglinide, repaglinide
281
meglitinides clinical use
Monotherapy in type 2 DM or combined with metformin
282
meglitinides SE's
Hypoglycemia (increased risk with renal failure) + weight gain
283
GLP-1 analogs
exenatide, liraglutide (sc injection)
284
GLP-1 analogs MOA
increase glucose-dependent insulin release, decrease glucagon release, decrease gastric emptying, increase satiety
285
GLP-1 analogs SE's
Nausea, vomiting, pancreatitis; modest weight loss
286
DPP-4 inhibitors
Lingaliptin, saxagliptin, sitagliptin
287
DPP-4 inhibitors MOA
Inhibit DPP-4 enzyme that deactivates GLP-1, thereby increasing glucose-dependent insulin release, decreasing glucagon release, decreasing gastric emptying, and increasing satiety.
288
DPP-4 inhibitors SE's
mild urinary or respiratory infections; weight neutral
289
Amylin analogs
pramlintide (sc injection)
290
Amylin analogs MOA
decrease gastric emptying = decrease glucagon
291
Amylin analogs SE's
Hypoglycemia in setting of mistimed prandial insulin + nausea
292
Amylin analogs clinical use
DM1 and DM2
293
Sodium-glucose co-transporter 2 (SGLT-2) inhibitors
Canagliflozin, dapagliflozin, empagliflozin
294
Sodium-glucose co-transporter 2 (SGLT-2) mechanism
Block reabsorption of glucose in PCT
295
Sodium-glucose co-transporter 2 (SGLT-2) SE's
glucosuria + UTIs + vaginal yeast infections + hyperkalemia + dehydration (orthostatic hypotension)
296
PPAR--gamma
Genes regulate fatty acid storage and glucose metabolism. Activation increases insulin sensitity + increases levels of adiponectin
297
alpha-glucosidase inhibitors
acarbose + miglitol
298
alpha-glucosidase inhibitors MOA
Inhibit intestinal brush-border alpha-glucosidases. Delayed carbohydrate hydrolysis and glucose absorption, thus decreasing postprandial hyperglycemia.
299
alpha-glucosidase inhibitors SE's
GI disturbances
300
thionamides
PTU + methimazole
301
PTU pnemonic
Ptu blocks Peripheral conversion
302
thionamide safe for pregnancy
PTU
303
Drug to use to control uterine hemorrhage
oxytocin
304
octreotide uses
1) acromegaly
2) carcinoid syndrome
3) gastrinoma
4) glucagonoma
5) esophageal varices
305
Glucocorticoids mechanism
1) Most effects mediated by interactions with GC response elements.
2) inhibite phospholipase A2
3) inhibite transcription factors, such as NF-kappaB
306
GC's SE's
1) iatrogenic cushing syndrome
2) adrenocortical atrophy (when stopped abruptly after chronic use)
3) peptic ulcers
4) peptic ulcers
5) steroid diabetes
6) steroid psychosis
7) cataracts
307
fludrocortisone
synthetic analog of aldosterone with little GC effects
308
fludrocortisone clinical use
Mineralocorticoid replacement in primary adrenal insufficiency
309
fludrocortisone AE's
similar to GC's + edema, exacerbation of HF, hyperpigmentation
310
cinacalcet MOA
sensitizes Ca2+ sensing receptor (CaSR) in parathyroid gland to circulating Ca2+
311
cinacalcet clinical use
primary or secondary hyperparathyroidism
312
cinacalcet AE's
hypocalcemia
