Assessment 4 Flashcards
(263 cards)
1
Q
Classic endocrine glands
A
Pituitary
Adrenal
Thyroid
PTH glands
2
Q
Atypical endocrine glands
A
GI
Adipose
Kidney, heart, liver,
3
Q
Classes of hormones
A
Peptide/protein
Steroid
Amine
4
Q
Steroid hormone precursor
A
Cholesterol
5
Q
Amine hormone precursor
A
Tyrosine or Tryptophan
6
Q
Hormone receptor types
A
Ion channel linked
Enzyme linked
Nuclear receptor
7
Q
Regulation of hormone production
A
Biosynthesis regulation
Precursor processing
8
Q
Regulation of hormone secretion
A
Feedback loops
Cyclical variation
9
Q
Protein binding
A
Extends half life of hormone
Protect from degradation
Solubilize lipophilic compounds
10
Q
Hormone clearance
A
Hepatic clearance/metabolism
Renal filtration
receptor mediated endocytosis
11
Q
Target tissue hormone regulation
A
Receptor population
Upregulation vs downregulation of receptors
Only tissues with specific receptors will respond
12
Q
Pituitary gland anatomical location
A
Inferior to hypothalamus
Enclosed in sella turcica
13
Q
Parts of Pituitary gland
A
Anterior: Adenohypophysis
Posterior: Neurohypophysis
Connected to hypothalamus via pituitary stalk
14
Q
Median eminence
A
Inferior border of hypothalamus
15
Q
Posterior PG embryology
A
Arise from diencephalon
16
Q
Anterior PG embryology
A
Arise from oral ectoderm
Envagination = rathke’s pouch
Normally loses connection to oral ectoderm
17
Q
Rathke’s cysts
A
Usually benign
18
Q
Craniopharyngioma
A
Benign and rare
Headache, vision issues, hormone deficiency
Surgery or radiation
19
Q
Anterior PG blood supply
A
Parvocellular neurons from hypothalamus, end at median eminence
Hormones secreted into portal vessels which act on anterior PG
20
Q
Posterior PG blood supply
A
Magnocellular neurons extend from hypothalamus into PPG
Synthesize and secrete ADH and Oxytocin and store in PPG
21
Q
Hypothalamic pituitary GH axes
A
Hypothalamus (GHRH) –> APG (GH) –> Liver (IGF-1)
22
Q
Hypothalamic pituitary Thyroid axes
A
Hypothalamus (TRH) –> APG (TSH) –> Thyroid (T3, T4)
23
Q
Hypothalamic pituitary adrenal axes
A
Hypothalamus (CRH) –> APG (ACTH) –> Adrenal (Cortisol)
24
Q
Hypothalamic pituitary gonadal axes
A
Hypothalamus (GnRH) –> APG (LH/FSH)
25
Prolactin
Promotes alveolargenesis during pregnancy
Post partum: Milk synthesis/secretion
Estrogen = (+)
Dopamine = (-)
Negative feedback on itself
26
Prolactinoma
Most common pituitary adenoma
Pharmacological intervention: Dopamine agonists
27
Sheehan syndrome
Complication of post partum hemorrhage
APG enlarged but blood supply same during pregnancy --> infarction from hypovolemic shock due to hemorrhage
28
Sheehan syndrom presentation
Acute: fail to lactate, hypotension, tachycardia
Chronic/Late: Amenorrhea, hypothyroidism
29
ADH
Vasopressin
Increase water permeability in kidneys: V2 receptor, aquaporin channel
Vascular smooth muscle contraction: V1 receptor
30
Oxytocin
Milk ejection
Uterine contraction
Stimulated by suckling, infant, orgasm
31
Action of growth hormone - Liver
Increase RNA, protein, glucose, IGF synthesis
32
Action of growth hormone -adipose
Lipolysis
| Decrease glucose uptake
33
Action of growth hormone - muscle
Increase AA uptake and protein synthesis
34
IGF action
Increase organ size/function
Linear growth
Increase lean body mass
35
Categories of GH secretory factors
1. Hormones
2. Neural
3. Metabolic
4. Pharm
5. Other
36
GH and metabolism
Fasting/starving or decreased glucose concentration = more GH
Increase glucose = low GH
37
Gonadotroph
Clinically non function pituitary adenoma, gonads
38
Thyrotrophs
Central hyperthyroidism or clinically non functioning
39
Lactotrophs
Hyperprolactinemia
40
Somatotrophs
Acromegaly
41
Corticotrophs
Cushings
42
Hyperprolactinemia clinical mainifestations
Decrease LH/FSH via GnRH inhibition
Infertility/galatctorrhea/amenorrhea
Impotence, decreased libido (men)
43
Gigantism vs acromegaly
GH excess
```
Acromegaly = epiphyseal closure
Gigantism = no closure
```
44
Acromegaly diagnosis
IGF-1
45
Acromegaly treatment
Somatostatin analog (GH inhibitor)
GH receptor antagonist
Radiotherapy
46
Cushings syndrome vs disease
Syndrome: Symptoms caused by prolonged exposure to glucocorticoids
Disease: Pituitary corticotroph adenoma
47
Cushings disease
Hypersecretory Corticotroph adenoma causing excess adrenal secretion
Fat face/body
Excess ACTH
48
Cushings diagnosis
24hr urinary free cortisol
Late night salivary cortisol
Dexamethasone suppression test
49
Thyrotropin secreteing pituitary adenoma
Lab: High free T4 and T3, abnormally high TSH
Weight loss, diarrhea, tremors, palpitations/tachycardia
50
TSH deficiency signs/symptoms
Decrease in energy
Growth retardation
Constipation
Weight gain
51
Hypopituitarism treatment
Relief of mass effect
Replacement of hormones
52
Central diabetes insipidus
Excessive free water loss due to lack of ADH
53
21 alpha hydroxylase deficiency
Most common CAH (90-95% of cases)
1. Decreased cortisol
2. Increased androgens in utero (virilization of female fetus)
3. Decreased aldosterone --> salt wasting. Decreased Na and increased K
54
11 beta hydroxylase deficiency
2nd most common CAH
1. Decreased cortisol
2. Increased mineralocorticoid activity (high 11-DOC)
3. Increased androgens in utero
Either 1+2 or 1+2+3
Diagnose with increased 11 DOC in urine
55
Lipoid CAH
Rare CAH
Defect in P450scc or StAR
Buildup of cholesterol
56
Vasopressin hypofunction
Diabetes insipidus: cannot excrete concentrated urine
Neoplasm
Inflammation
Head trauma
57
Vasopressin hyperfunction
SIADH: Cannot excrete dilute urine --> hyponatremia and volume expansion
Ectopic secretion from tumors
58
Conn syndrome
Primary aldosteronism with hypertension and unprovoked hypokalemia
Suppression of renin
Most commonly due to aldo secreting adenoma
59
CAH
Congenital adrenal hyperplasia
Cortisol deficiency and ACTH increase
90% cases associated with 21 hydroxylase deficiency
60
Adrenal cortical carcinoma
Rare neoplasm
Necrosis and hemorrhage
Invasion of adjacent structures: IVC, adrenal vein
61
Adrenal gland hormones: medulla
Catecholamines
62
Adrenal gland hormones: cortex
Mineralocorticoids
Glucocorticoids
Androgens
63
Zona glomerulosa hormones
Mineralocorticoids
64
Zona fasciculata hormones
Glucocorticoids
65
Zona reticularis hormones
Androgens
66
Aldosterone function
Salt/water retention
| K excretion
67
Primary aldosteronism
Aldosterone production is abnormally high
68
Primary aldosteronism physiological symptoms
HTN
Hypokalemia and mild hypernatremia
Mild metabolic alkalosis
69
Primary aldosteronism causes
Aldo producing adrenal adenoma (APA)
Adrenal hyperplasia (IHA, BAH, UAH)
Familial hyperaldosteronism
70
Screening test for primary aldosteronism
PAC/PRA > 20 = (+)
71
Primary aldosteronism confirmation tests
Oral sodium loading
IV NS load
Fludicortisone suppression
Check to see if aldo is suppressed
72
Primary aldosteronism subtype classification tests
CT: Can test cause (adenoma, hyperplasia, carcinoma) but not source
Adrenal vein sampling: Compare aldo from both sides, can find source
73
Right vs left adrenal vein
Right: Short and small. Directly enters IVC
Left: Tributary to real vein, easy to cannulate
74
Adrenal vein sampling results
Aldosterone concentration/Cortisol concentration
4:1 = unilateral
75
APA/IHA treatment
Surgery in good candidates
76
IHA/GRA treatment
Minrealocorticoid receptor blocker - Spironolactone
Secondary antihypertensive
77
Pheochromocytoma and Paraganlioma
Paraganglioma arise from autonomic ganglia, outside of adrenal glads
Excess production of epi and norepi
78
Pheochromocytoma and Paraganlioma incidence
90% adrenal
90% unilateral
90% benign
15-20% familial
79
Paraganglioma stats
Norepi excess
30% malignant
25% extra abdominal
80
Presentation of Pheochromocytoma
```
Pain
Pressure (HTN)
Perspiration
Pallor
Palpitations
```
81
Pheochromocytoma diagnosis
Metanephrine plasma level
24hr urinary metanephrine, fractioned catecholamines
82
Pheochromocytoma radiology
CT scan
MIBG: Compound that resembles Norepi, scan can detect tumors
83
Adrenal failure clinical presentation
Hyperpigmentation: Skin, buccal cavity, scars
Postural hypotension
Addisonian crisis
Nausea/vomiting
84
Hyperpigmentation w/ primary adrenal insufficiency?
Melanocyte stimulating hormone and ACTH on part of same protein
85
Adrenal failure lab findings
Hyperkalemia, hyponatremia, hypoglycemia
Lymphocytosis, eosinophilia
Adrenal autoantibodies if auto immune disease
86
Primary adrenal failure
Addisons
Decreased aldo and decreased cortisol, issue with adrenal gland
Hyperkalemia, hypotension
Increase ACTH
87
Secondary/tertiary adrenal insufficiency
Normal aldo, less prominent hypotension
Decreased ACTH, no hyperpigmentation
88
Primary adrenal insufficiency etiology
```
Autoimmune
Infection
Cancer
Adrenal hemorrhage
CAH
```
89
Secondary adrenal insufficiency etiology
Glucocorticoid withdrawal
Hypopituitarism via radiation, surgery, mass
90
Low cortisol + Low ACTH =
Secondary adrenal insufficiency
91
Low cortisol + High ACTH =
Primary adrenal insufficiency
92
Most common CAH enzyme deficiencies
21 hydroxylase
11B hydrolxylase
17a hydroxylase
93
21 a hydroxyalse deficiency symptoms
Virilizing + Salt wasting
94
Cortisol and metabolism
Gluconeogenesis and glucose storage, decrease glucose breakdown
Lipolysis but also increase appetite
95
ACTH independent vs dependent Cushings
Dependent: Cushings disease
Ectopic ACTH
Ectopic CRH
ACTH independent: Adrenal adenoma/carcinoma/hyperplasia
Exogenous steroids
96
Thyroid blood supply
Superior thyriod artery
Inferior thyroid artery
Lowest thyroid artery
- Branch of brachiocephalic trunk, present in 5-10%
97
Recurrent Laryngeal nerves
Innervate muscles of larynx, open/close vocal cords
98
T3 and T4 action
T3 is better ligand for receptor
T4 is negative feedback on hypothalamus
99
T3/4 synthesis
1. Iodide uptake via NIS
2a. Thyroglobulin synthesis and exocytosis into follicle - not driven by TSH
2b. Free iodide transported into follicle by Pendrin
- Iodide oxidized by TPO to iodine
3. Iodination of thyroglobulin = MIT and DIT
- TPO
4. TSH stimulated conjugation of iodinated tyrosines to make T3 and T4
5. Endocytosis of iodinated thyroglobulins, lysoendosome formed
6. Proteolysis in lysoendosome releases T3, T4, RT3. MIT/DIT recycled
7. Secretion into circulation
100
DIT + DIT =
T4
101
MIT + DIT =
T3, most active
102
DIT + MIT =
reverse T3
Useless sack of shit
103
Thyroid transport proteins
Thyroxine binding globulin (TBG) - T3, T4
Trasnthyretin - Thyroxine
104
Calcium sensing receptor
Highly expressed on chief cells of parathyroid gland
Sense serum Ca concentration
105
Vit D
Diet or synthesized via cholesterol
106
Vit D and Ca
Vit D increases Ca transport proteins in duodenum
107
PTH synthesis
Prohormone, processed in golgi
PTH increases serum calcium
108
PTH and bone
Induces RANK ligand and M-CSF on osteoblasts
Activate osteoclast precursor cells which become osteoclasts --> eat up bone and release Ca
109
PTH and kidney
Ca reabsorption in DCT and CCD
110
PTH related protein
PTHrP
Binds PTH receptor, mobilize Ca to produce milk
Mediates osteolytic bone metastasis
111
Calcitonin
Less bone resorption and decreased Ca released
112
Mutations in CaSR
Inactive: Hypercalcemia/hypocalciuria
Active: Hypocalcemia
113
Leptin
Produced in fat
Circulating levels signal to brain how much fat is in system
114
Melanocortin system
alpha-MSH (agonist) and AgRP (antagonist)
AgRP = increased feeding/body weight
a-MSH = reduced feeding and body weight
115
Diet and melanocortins
Diet = aMSH down and AgRP up
116
Leptin deficiency and melanocortins
MSH down
AgRP up
117
High fat leptin pathway
Leptin activates POMC --> MC4 receptor --> decreased weight
Inhibits AgRP
118
Low fat leptin pathway
Low leptin does not stimulate POMC, less AgRP inhibition --> Activate Y1/Y5 --> Increase weight
AgRP also inhibits MC4 receptor
119
Leptin and thyroid function
Leptin is positive regulator of TRH
Increase Leptin = increase Thyroid
120
Leptin and gonads
Positive regulator
Increase leptin = increase LH/FSH
121
Environmental causes of obesity
Genetics modified by environment
Obesogenic environment: Inactivity and readily available food supply (increased portions, energy dense)
122
Obesity guidelines: Waist circumference
Measure in pts with BMI of 25-34.9
>35in (female)
>40in (males)
Estimate of visceral fat
123
Obesity guidelines: Assess and treat CV risk factors and comorbidities
Weight loss vs maintenance
Weight loss: Overweight + 1 or more CV factor OR obese
Weight maintenance: Normal weight, overweight w/o comorb, overweight/obese but cant lose weight
124
Obesity guidelines: Recommend goals for weight loss
Initial goal: 10% weight loss in 6 months
Rate of weight loss:
.5-1 lb/week BMI (27-34.9)
1-2 lb/week (BMI>35)
125
Obesity guidelines: Recommend method for weight loss
Weight loss with both low carb and low fat diets
Diets should be tailored to individual patients
126
Obesity guidelines: Comprehensive lifestyle interventions
1200-1500kcal/day for females
1500-1800 kcal/day for men
500-700kcal/day energy deficit + increased activity
127
Acceptable macronutrient Distribution range
Carb: 45-65%
Protein: 10-35%
Fat: 20-35%
128
Thyroid hypofunction histology
Atrophic follicles
| Mononuclear cell infiltration with germinal centers
129
Subacute thyroiditis
Granulomatous (painful)
Lymphocytic (painless)
130
Riedels thyroiditis
Rare, fibrotic
131
Acquired thyroid hypofunction
Post therapy for hyperthyroidism or thyroid neoplasms
132
Thyroid hyperfunction
Thyrotoxicosis
Increased production or increased release of pre formed hormone from damaged thyroid gland
133
Hyperthyroidism (increased production)
Autoantibody that mimics TSH (Graves)
Excess TSH or TRH (very rare)
Secretion by neoplasm
134
Thyroid storm
Life threatening
Fever, delirium, seizures, vomiting
Death from cardiac arrhythmia/failure
Treat by block T4--> T3 conversion
135
Nodular hyperplasia
Usually euthyroid
Dominant nodule may emerge, simulate neoplasm
Iodine deficiency
Dietary goitrogens
136
Thyroid anaplastic carcinoma
Aggressive tumor in elderly
Kills by direct invasion of airway
May have p53 loss
137
RAS point mutation cancer
Fillicular and anaplastic carcinoma
138
PTEN point mutation
Follicular and anaplastic carcinoma
139
BRAF point mutation
Papillary carcinoma
140
RET gene mutation
Papillary carcinoma
| Medullary carcinoma
141
Hypoparathyroidism most common cause
Surgical excision of parathyroid gland
142
Hypoparathyroid causes
Surgery
Congenital agenesis/hypoplasia
Autoimmune
Mg deficiency
143
Hypoparathyroid biochemical features
Low PTH
Low Ca
High phosphorus
144
Hypoparathyroid clinical features
Increased neuromuscular excitability
Emotional disorders
Parkinson like syndrome
Basal ganglia calcification
145
Hyperparathyroidism causes
Adenoma (80%)
Hyperplasia (15%)
3% of all cases associated with MEN I or IIa
146
Secondary hyperparathyroidism causes
Chronic renal insufficiency
Vit D deficiency
Intestinal malabsorption
147
Secondary hyperparathyroidism and renal failure
Renal retention of phosphorus + loss of Ca
Reduced 1,25(OH) Vit D resulting in decreased Ca absorption
148
Advanced hyperparathyroidism
Severe kidney stones
Osteitis fibrosa
149
Malignancy associated hypercalcemia
80% due to direct invasion of bone by tumors
20% attributed to PTHrP: Blocks osteoprotegrin secretion by osteoblasts --> Promotes osteoclastogenesis
150
pH and Calcium serum concentration
Alkalosis = increase in albumin bound Ca but decrease in free Ca
Acidosis = Decrease in albumin bound Ca but increase in free Ca
Lower pH = Decreased albumin affinity for Ca
151
Hypercalcemia clinical presentation
Kidney Stones
Bones - osteitis fibrosa, fractures
Moans - lethargy, depression
Ab Groans - constipation, peptic ulcer
152
Osteitis fibrosa
Increased osteoclasts
increased bone resorption
153
Hypercalcemia diagnosis
Check serum Ca
Check PTH level
Measure 24hr urinary Ca after repleting Vit D to rule out FHH
154
HyperPTH treatment
PTH surgery
Bisphosphonates: Anti resorptive agents (bone protection)
Cinacalcet: Decrease serum Ca level (symptomatic hypercalcemia)
155
Hypocalcemia pathogenesis
Deficiency Vt D supply/action
Deficient PTH synthesis/secretion
156
Normal Vit D level and required amount
>30ng/mL
Need ~2000IU
157
Imparied PTH secretion causes
Antibody inhibition
CaSR activating mutation
Hyper/hypomagnesemia
PTH gene mutations
158
DiGeorge Syndrome clinical pres
```
Cardiac
Abnormal fascies
Thymic aplasia
Cleft palate
Hypocalcemia with 22q11 deletion
```
159
Hypocalcemia and neuromuscular
Lower threshold to nerve conduction = spasms, cramps, weakness
160
Chvosteks sign
Hypocalcemia
Press on cheek = twitch of face
Response = degree of hypocalcemia
161
Trousseau's sign
Place BP cuff on upper arm --> carpopedal spasm
162
Treatment of hypocalcemia
Raise serum Ca to low-normal range
Avoid hypercalciuria
IV Ca, oral Calcitrol
Vit D, maybe Mg
163
Lobectomy/hemi thyroidectomy
Removal of one lobe
Diagnostic for suspicious nodules
Toxic adenoma
164
Total/near total thyroidectomy
Removal of entire thyroid - leave small remnant near nerve/PT
Cancer, graves
165
Thyroid surgery complications
Recurrent laryngeal nerve injury: Unilateral = hoarse, bilateral = airway obstruction
Superior laryngeal nerve injury: Loss of high pitch
Hypocalcemia/hypoPTH
Hemorrhage - cut open to prevent airway obstruction
166
Neck/Node dissection: Central
Level VI
Initial lymph drainage of thyroid
Elective or therapeutic: Positive or negative nodes
167
Neck/Node dissection: Lateral
Levels I-V
Secondary lymph drainage of thyroid - Jugular, transverse cervical
Therapeutic - positive for nodes
168
PTH surgery
Unilateral: sporadic primary hyperPTH
Bilateral: Both sides, non localized primary hyperPTH, hereditary (MEN1, MEN2a)
Secondary/tertiary hyperPTH
169
Indications for PT surgery
Bones
Stones
Muscle weakness
170
Parathyroid embryology: Inferior
3rd pharyngeal pouch
Descend with thymus
Anterior to recurrent laryngeal nerve
171
Parathyroid embryology: Superior
4th pharyngeal pouch
| Posterior to recurrent laryngeal nerve
172
Primary HyperPTH MEN
MEN1: hyperplasia
MEN2a: multiple adenomas
173
Minimally invasive/unilateral parathyroidectomy benefits
Reduced risk
Positive preop localization
High cure rates
174
Intraoperative PTH assay
Helps in deciding when to stop procedure
Pre incision and pre removal level with post removal
80% reduction = specific
50% reduction = sensitive
175
Pancreatic islet cell types
Beta cells - Insulin
Alpha cells - Glucagon
Delta cells
176
Proinsulin --> insulin
Proinsulin cleaved to insulin (A+B) and C peptide
177
Incretin effect
GLP-1 and GIP - gut hormones
Dietary glucose --> GLP-1/GIP activation --> insulin secretion/glucagon inhibition
178
Insulin action
Insulin binds to receptor --> MAP kinase pathway --> Glucose transporter to membrane
179
Low glucose effect
Low glucose --> Decreased ATP/ADP --> KATP channel open --> weak Hyperpol --> Ca channel open --> Ca increase glucagon secretion
180
High glucose effect
High glucose --> ATP/ADP increase --> KATP channel close --> depol --> no glucagon release
181
Type I diabetes overview
Morbidity and mortality
Autoimmune destruction of islets
Absence of insulin
Genetic+environment
No cure
182
Type I Diabetes autoimmunity
Selective destruction of islet Beta cells
Circulating antibodies to islet cell antigens
Linkage with MHC genes
T cell mediated beta cell destruction
183
T cell mediated Type I DM
Infiltrating CD4+, CD8+ T cells
anti T cell therapies are effective
184
Genetic factors of T1D
MHC Class II locus
Defects in immunomodulation
Attack own cells
185
DCCT results
Control of blood glucose works with intensive treatment - But difficult therapy
186
Hypoglycemia
Rate limiting factor for T1D treatment
Severe hypoglycemia sees unawareness of symptoms
187
Causes of hypoglycemia
Absolute excess insulin: Before lunch/dinner, predawn, gastroparesis
Relative excess: Exercise and alcohol
188
Exercise and glucose
Increase exercise = glucose into tissues = hypoglycemia risk
189
T1D routine management
```
HA1c multiple times a year
Foot exams/neuropathy testing
Renal monitoring
Retinal exams
Lipids
BP
```
190
LADA
Latent autoimmune diabetes of adulthood
In between DM1 and DM2
Variable auto immune function, metabolic syndrome, insulin resistance
191
Diabetic ketoacidosis
Hyperglycemia
Acidosis
Volume depletion
Electrolyte abnormalities
192
Diabetic ketoacidosis management
Volume replacement
Insulin
Electrolyte balance
Education
193
Diabetic ketoacidosis pathogenesis
Decrease in insulin: Increase glucose, decreased glucose uptake --> hyperglycemia = osmotic diuresis
Increased FFA release, increased ketogenesis = ketoacidosis
194
DKA symptoms and signs
Symptoms: Polyuria, weakness, weight loss, nausea, vomiting
Signs: Tachycardia, hypothermia, ileus, acetone breath, altered sensorium, Kussmaul (deep, frequent) breaths
195
Prognostic factors of DKA
Hypotension
Age over 65
Altered mental status
196
DKA management
```
Hydration
IV insulin
Monitor K
Bicarb for extreme cases
Prevent recurrence: Education
```
197
Primary hypothyroidism etiology
Autoimmune
Thyroidectomy
Iodide deficiency
Drugs
198
Secondary hypothyroidism etiology
Hypopituitarism
| Hypothalamic damage
199
Clinical manifestations of hypothyroidism
```
Weakness
Lethargy
Slow speech
Cold intolerance
Constipation
Weight gain
Hair loss
Edema
Decreased perspiration - dry skin
```
200
FT4 normal
| TSH normal
Euthyroid
201
FT4 low
| TSH High
Primary hypothyroidism
202
FT4 low
| TSH normal/low
Secondary hypothyroidism
203
Subclinical hypothyroidism
T4 normal
Slightly high TSH
Few or no symptoms
204
Hypothyroidism therapy
Treat with hormone replacement
LT4 pills = synthetic T4
Check TSH 6-10 weeks
Target is TSH level
205
Thyroxine dosage
Higher weight = higher dose
Old patients on lower dose
Ca, Fe, soy can block absorption
Malabsorption = higher doses
Estrogen, antidep, anti seizure = increase requirement
206
Hypothyroidism in pregnancy
Thyroxine is safe
Dosage increases during pregnancy
Baby cant make thyroid hormone during first trimester
Important to keep regulated during pregnancy
207
Thyroid autoimmunity
Most common cause of hypothyroidism
Graves disease
Anti TPO antibodies (Hashimoto)
TRAB and TSI (Graves)
208
Thyrotoxicosis etiology
Graves
Toxic Adenoma
Subacute/silent thyroiditis
TSH secreting adenoma
Factitious/Iatrogenic (taking thyroid hormone)
209
Graves disease
Autoimmune hyperthyroidism
Female predominance
Associated opthalmopathy
210
Clinical manifestations of Graves
```
Nervous
Fatigue
Weakness
Heat intolerance
Tremor
Hyperactivity
Palpitations
Increase appetite
Weight loss
```
211
Lid lag
Hyperadrenergic effect of thyrotoxicosis
212
Graves opthalmopathy
Eyes bulge forward, eyelid retraction
Autoimmune response against orbital auto antigen shared by thyroid
213
Toxic multinodular goiter
2nd most common cause of hyperthyroidism, most common in elderly
Dysphagia, hoarseness, shortness of breath
214
Thyroiditis: Subacute and Silent
Acutre destruction of thyroid tissue, leakage of hormone
Subacute: painful, viral illness
Silent: post partum, painless, pre existing autoimmune
215
TSH secreting pituitary adenoma
Rare
Macroadenoma
Elevated T4
Inappropriately normal TSH
216
Factitious thyrotoxicosis
Due to ingestion of thyroid hormone
Serum thyrogolubulin used for diagnosis
Exogenous thyrotoxicosis: low thyroglobulin
Destructive thyroiditis: high thyroglobulin
217
Increased radio iodine uptake = ?
Graves
Toxic MNG
Toxic adenoma
218
Decreased radio iodine uptake = ?
Thyroiditis
Exogenous thyroid hormone
Iodinated contrast
219
Thionamides
Treatment for hyperthyroidism
Methimazole and PTU block thyroid hormone formation - Block TPO
PTU decreases T4-->T3 conversion
220
Radioiodine treatment
Preferred treatment
NOT in pregnancy
Eventual hypothyroid
221
Sick Euthyroid Syndrome
Decrease in T3/T4/TSH but increase in rT3
Decreased 5 deiodinase
Decreased TBG
Plasma inhibitors to binding
Increased TBG
Decrease uptake of thyroid hormones
222
Pheochromocytoma treatment
Adrenalectomy - high risk, need to prepare
223
Cushings disease clinical presentation
Thin skin, acne, bruising, hirtuism
Hypertension
Depression
Moonface, buffalo hump, truncal obesity, thin limbs
Hyperglycemia, osteoporosis, hypokalemia
224
Cushings treatment
Transsphenoidal surgery -- Pituitary irradiation --> Total bilateral adrenalectomy
225
Adrenal tumor disease treatment
Surgical resection --> Mitotane therapy --> Surgery of recurrent tumor --> Enzyme inhibitors
226
Ectopic ACTH syndrome treatment
Surgical resection --> Adrenal enzyme inhibitor --> Medical/surgical adrenalectomy
227
Epidemiological determinants of T2DM
Genetic risk factors
Demographics
Behavioral/lifestyle
MEtabolic determinants
Intermediate risk categories: insulin resistance, glu inteolerance
228
Diagnostic testing for diabetes
Fasting blood glucose: Normal 200
Random plasma glucose: >200
HbA1C: Normal 6.5%
229
HbA1C
Measure of glucose binding to Hb in blood
Accurate representation of 3 months glu level
230
T2DM organ pathophysiology: Liver, Muscle, Adipose, Pancreatic islet
Liver: Increased hepatic Glu production
Muscle: Decreased Glu uptake
Adipose: High lipolysis even with increased insulin
Islet: Glucagon high after meal, insulin doesn't increase as much
231
Ominous octet
1. Increased hepatic production of glucose
2. Decreased incretin effect
3. Increased lipolysis
4. Increased kidney Glu reabsorption
5. Decreased Glu uptake by muscle
6. Neurotransmitter dysfunction
7. Increased glucagon secretion
8. Impaired insulin secretion
232
Natural history of Type 2 diabetes and Beta cell function
Insulin resistance increases
Genetic Beta cell dysfunction increases over time and eventually reaches failure
233
Mechanisms of insulin resistance
```
Elevated FFA
Increase muscle TG
Abnormal mitochondrial function
Hyperinsulinemia
Inflammation and TNFa
Hyperglycemia
Lipodystrophy
```
234
Lack of insulin and lipids
Adipose metabolism without insulin inhibition = elevated TG, reduced HDL, small dense LDL particles
Atherogenic
235
Treatment of diabetes goals
HbA1C target less than 7%
Diet/lifestyle modification
Medication
Manage CV risks
236
Diet recommendations for T2DM
Caloric restriction for obesity
Limit CHO to 45-60g
Limited saturated fat
Increase dietary fiber
237
Gestational diabetes
Glucose intolerance during pregnancy
7-10% pregnancy
Progressive insulin resistance
Failure of beta cell compensation
238
Gestational DM diagnosis
Screening: Glucose challenge
100g OGTT if over threshold of glucose challenge
239
SGLT2 Inhibitor
Blocks reabsorption of glucose in kidney
Dapaglifozin
240
Thiazolidinidiones
Activate PPAR-gamma
Decrease FFA, increase insulin sensitivity
CHF issues
Weight gain
241
Secretagogues
SUR-1 activator: Block KATP channel --> insulin release
Sulfonylureas - Glipizide. Cheaper/lower dose
Meglitinide - Nateglinide
Weight gain, hypoglycemia
242
Biguanides
Metformin
Activate AMPK = increase glucose uptake by muscle/decrease hepatic gluconeogenesis
Lactic acidosis, GI issues
243
DPP4 inhibitor
Slow degradation of GLP-1/GIP
Sitagliptin, Linagliptin
Well tolerated, high cost
244
Alpha glucosidase inhibitor
Block CHO digestion (final step)
Acarbose
Diarrhea/flatulence
245
GLP-1 agonist
Increase GLP-1
Dulaglutide
Weight loss, GI, Injection
High cost
246
Amylin mimetics
Activate amylin receptor: Decrease glucagon, decrease gastric emptying, increase satiety
Weight loss
Decrease post prandial glucose
High cost
Pramlintide
247
Bile acid sequestrants
Bind bile acid
Decrease hepatic glucose production
High cost
Colesevelam
248
Dopamine-2 agonists
Modulate hypothalamic control of metabolism
Increase insulin sensitivity
High cost
Bromocriptine
249
Hyperglycemic damage to tissue (4)
1. Increased accumulation of AGE's
2. PKC activation
3. Aldose Reductase pathway acceleration
4. Hexosamine pathway increase
250
Accumulation of AGE
Advanced glycosylated end products
Can diffuse out of cell and damage ECM and alter albumin
Results in pro inflammatory cytokines and growth factor
251
PKC activation
Induces PKC pathway
Increase blood vessel constriction
Blood vessel leakiness/angiogenesis
Clot formation and slowing of anti coagulation
Proinflammatory gene expression
252
Aldose Reductase acceleration
High glucose is converted to sorbitol by aldose reductase
Enzyme can't be used to generate glutathione
Low glutathione = increased oxidative stress
253
Hexosamine pathway
Glu --> Fru --> F6P --> N acetyl glucosamine
N acetyl glucosamine can alter gene expression and result in pathology of damaging blood vessels
254
Unifying mechanism for hyperglycemia and tissue damage
Glucose --> ROS --> PARP --> Decrease GAPDH --> 4 pathways of tissue damage
255
Macrovascular damage mechanism
Increased FFA --> ROS --> PARP --> etc etc
256
Diabetic microangiopathy
Diffuse thickening of Basement Membrane
Distortion, abnormal permeability, eventual occlusion of capillaries
257
Diabetic retinopathy (2 types)
Background (Non proliferative) Retinopathy
Proliferative Retinopathy
258
Non proliferative Diabetic retinopathy
Mild -- Moderate -- Severe
Microaneurysms, hemorrhages, exudates
Macular edema
259
Proliferative Diabetic retinopathy
Neovascularization
Pre retinal hemorrhages
Fibrovascular tissue proliferation
Macular edema
260
Diabetic Nephropathy
Damage to vessels in renal system
Glomerulosclerosis, thickening of BM, nodular glomerulosclerosis
Nephrotic
261
5 Stages of Diabetic Nephropathy
1. Hyperfunction/hypertrophy
2. Silent stage - BM thickened
3. Incipient stage - microalbuminuria
4. Overt Diabetic nephropathy - macroalbuminuria
5. Uremic - ESRD
262
Diabetic peripheral neuropathy
Nerve damage/destruction
Pain and sensory loss
263
5 Major factors of Diabetic foot
1. Neuropathy
2. Peripheral artery disease
3. Ulceration
4. Infection
5. Impaired wound healing
