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Flashcards in Endocrinology Deck (312):
1

Most common ectopic thyroid tissue site

tongue (lingual thyroid). removal may result in hypothyroidism if it is the only thyroid tissue present.

2

branchial cleft cyst origin

persistent cervical sinus

3

Thyroid tissue origin

endoderm

4

parafollicular cell origin

neural crest

5

adrenal cortex and medulla origin

cortex from mesoderm, medulla from neural crest

6

chromaffin cell regulatory control

preganglionic sympathetic fibers

7

Melanotropin (MSH) origin

Intermediate lobe of pituitary.

8

Anterior pituitary other name

adenohypophysis

9

Anterior pituitary origin

oral ectodrm (Rathke pouch)

10

Hormones that share alpha subunit

TSH, LH, FSH, and hCG. Beta subunit determines specificity.

11

proopiomelanocortin (POMC(

ACTH and MSH are derivates of proopiomelanocortin (POMC)

12

hormones of anterior pituitary

FLAT Pig: FSH, LH, ACTH, TSH, PRL, GH.

13

Basophils

B-FLAT: basophils-FSH, LH, ACTH, TSH

14

Acidophils

GH, PRL

15

posterior pituitary other name

neurohypophysis

16

Origin of ADH and oxytocin

supraoptic and paraventricular nuclei

17

ADH and oxytocin transport

carrier proteins called neurophysins.

18

posterior pituitary embryo origin

neuroectoderm

19

Islets of langerhans

collections of alpha, beta, and gamma endocrine cells in the pancreas.

20

Islets of langerhans origins

Arise from pancreatic buds.

21

Islets of langerhans organizations

alpha cells peripherally, beta cells centrally, delta cells interspersed

22

alpha cells secrete

glucagon

23

delta cells secrete

somatostatin

24

Insulin synthesis

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.

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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.

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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.

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Insulinoma treatment

surgical resection

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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