Week 4 (Exam 2) Flashcards
(253 cards)
1
Q
Cardiac support for patients unresponsive to conventional therapy until thyroid hormone normalization can be achieved
A
ECMO (extracorporeal membrane oxygenation)
2
Q
Autoimmune polyendocrine syndrome 2
A
Adrenalitis, thyroiditis, DMI
3
Q
Biggest causes of primary hyperparathyroidism
A
Adenoma is almost all of them
primary hyperplasia, 5-10%, parathyroid CA 1%
4
Q
MEN1
A
Primary hyperparathyroidism Pancreatic endocrine tumors Pituitary adenomas (lacto- or somatotrophin) Menin (MEN1) ts gene mutation Can also have duodenal gastrinomas
5
Q
Watch out for what in girls with delayed puberty or shortness
A
Karyotype (looking for 45 XO)
Turner’s comes with horseshoe kidney, CV defects
6
Q
Burch Wartofsky Score
A
Thyroid storm: Fever, Cardiac (tach, CHF), GI (diarrhea, jaundice), Precipitating Hx (pregnancy, hemithyroidectomy, amiodarone)
7
Q
Signs and sx of Hyperglycemic hyper osmotic syndrome
A
Glucose over 600 Severe dehydration Hyperosmolality (over 350) - obtundation, coma Impaired renal function NO KETONES
8
Q
Etiology of congenital adrenal hyperplasia
A
21-hydroxylase deficiency (steroidogenesis)
impaired feedback to hypothalamus/pituitary with resultant hyperplasia
9
Q
Amiodarone dosing
A
200mg tab with 74.4mg I with 7.4mg released qd as free
Daily recommended I is 0.15mg
You can see why this can be toxic
10
Q
Pseudohypoparathyroidism
A
Hypocalcemia, hyperphosphatemia despite high PTH
Physiology acts like its not even there
Resistance to PTH! related to G-protein receptor pathways, can affect other hormone paths (TSH,LH/FSH)
11
Q
Three main sources of hypopituitarism
A
Tumors (craniopharyngioma, Rathke’s, glioma)
Empty Sella
Sheehan: post partum necrosis of Anterior Pituitary
12
Q
Symptomatic vs Asx hypercalcemia
A
ASx means primary hyperparathyroidism
Sx means malignancy
13
Q
Leading cause of end stage renal disease in the US
A
Diabetic nephropathy. Screen it out with albumin:creatinine
14
Q
Radioactive I for thyroid cancer
A
Contraindicated in pregnant women, its meant to target and destroy the thyroid
15
Q
Sx of Non-ketotic hyperosmolar state
A
Polyuria, thirst, altered mental state
ABSENT n/v, abdominal pain, kussmaul respirations
16
Q
Hyperglycemic hyper osmotic syndrome
A
Acute hyperglycemic crisis in DMII
Culmination of prolonged insulin deficiency: Increased gluconeogenesis, decreased glucose uptake in peripheral tissues
17
Q
Parathyroid adenoma
A
Benign neoplasm of parathyroid chief or oxyphil cells
Typically solitary, maybe surrounded by rim of normal parathyroid tissue
Come from MEN mutations
18
Q
Pro-thyroid agents (4)
A
T4: Levothyroxine
T3: Liothyronine
Liotrix (4:1 mix of T4:T3)
Thyroid desiccated
19
Q
Insulin indicated for post-prandial hyperglycemia
A
Glulisine
Taken before meal as SQ injection
Onset 5-10 min, lasts 1-3 hr, peaks 0.5-1 hour
20
Q
Cells of the parathyroid
A
Chief Cells
Oxyphil Cells
Adipocytes
21
Q
Best practices for evaluating pediatric growth
A
<36 mo w/ 0-36mo curve: measure while supine (length)
>36 mo w/ 2-20y.o. curve: measure standing up (stature)
22
Q
K replacement in DKA
A
When serum K is below 5.5
Monitor for cardiac changes and verify urine output (probs need indwelling foley)
23
Q
DiGeorge Syndrome
A
22q11.2 deletion
possibly parathyroid under- or non-development
Causes hypocalcemia
Facial anomalies, “tet spell” cyanosis, tetany, infection
24
Q
Tertiary hyperparathyroidism
A
Prolonged hypocalcemia causing autonomous function of parathyroid glands
25
Fluid replacement protocol for DKA
2-3 liters normal saline (first 1-3 hrs)
then half-strength saline at 150ml/hr
Once glucose hits 250, switch to 5% dextrose 0.45% saline at 100-200ml/hr
26
Papillary thyroid carcinoma
Majority of malignant thyroid tumors, 25-50 years old
Usually Asx, palpable nodule, seen on US
Psammoma bodies, "orphan Annie eye nucleus" is Dx
RET-PTC and BRAF mutations
27
Levothyroxine MOA
Manufactured form of T4, converted to T3
Can take up to 6 weeks for max effect
Dosing based on regular TSH and T4 measurements
Sides: weight loss, sweating, anxiety, etc
28
Calciphylaxis
Secondary hyperparathyroidism causing calcification and occlusion of blood vessels with resultant ischemia
29
Signs and Sx of DKA
```
Abdominal pain, mental dysfunction, coma
Kussmaul (rapid/deep) Respirations
Fruity or nail-polish breath
Dry mucous membranes, poor skin turgor
Fluid deficit 3-5L (less than NKHS)
```
30
Anti-thyroid agents (4)
Radioactive iodine (131I) sodium
Methimazole
K-Iodide
Propylthiouracil (PTU)
31
Treat thyrotoxicosis (thyroid storm, symptomatic hyperthyroidism)
Non selective b-blocker (1 and 2): inhibit conversion of T4 to T3 (more biologically active version in periphery)
32
Somatostatinoma
Diabetes, cholelithiasis, steatorrhea
| Reduced insulin, reduced gallbladder motility, reduced exocrine pancreas secretions
33
What nerve transmits referred pain from the spleen to the shoulders?
Phrenic (Kehr's sign)
34
Presentation of DKA
Triad of hyperglycemia, ketonemia, metabolic acidosis
35
How does graves disease cause exophthalmos
lymphocytes invade preorbital space, fibroblasts there have TSH receptor. EOM swells, matrix accumulates, adipocytes expand
36
Metformin MOA
Activates AMP-activated protein kinase
| biguanide
37
Gliflozin clinical uses
Adults with DMII, taken orally before first meal qd
| Correct hypovolemia before starting this
38
Empty Sella Syndrome
Primary: SCF leaks into it, compresses pituitary
Secondary: Pituitary expands and infarcts within sella
39
Meglitinide clinical use
postprandial hyperglycemia, oral before meal
40
What is the purpose of radioisotope scanning goiters?
Determines if a nodule is responsible for hyperfunction
Cold nodules are more likely neoplastic (hot more likely to be benign), but US and fine needle aspiration are more useful
41
MEN2a
Pheochromocytoma
Medullary thyroid carcinoma
Parathyroid hyperplasia
Germline RET proto-oncogene GOF
42
Glulisine MOA
Mutations from human sequence block assembly of dimers and hexamers - allow for faster glucose absorption
43
C Cells
In the thyroid, make calcitonin
| NE carcinoma have amyloid, blue w/ chromatin
44
Sx of primary hyper parathyroidism
Painful Bones (osteoporosis/osteitis fibrosis cystica)
Renal Stones
Abdominal groans (constipation, stones)
Psychic moans (depression, lethargy, seizures)
These are mostly from protracted Hypercalcemia
45
Diagnostics of 21-hydroxylase deficiency
Heel stick the baby!
ACTH stimulation test
17-hydroxyprogesterone
46
Somatotroph pituitary adenoma histology
Like all adenomas there's diffuse growth. These can be mixed with PRL-secreting cells though
47
Hormone levels found in primary hyperthyroidism
Decreased TSH, Increased FT4
48
Steps of insulin release
GLUT-2 takes it into b-cells, generates ATP, inhibits K channel, causes Ca influx, causes insulin release
49
Glargine MOA
aa substitutions in both a- and b-chains enhance crystal stability, changing the pKa of insulin
for basal maintenance, 1-2 SQ daily
Onset 3-4 hours, lasts 24 hours, peakless
50
K-I MOA
Stable form of iodine, blocks its uptake
51
Labs of Grave's disease
T3/T4 high
TSH low
TSI (thyroid stimulating Ig) High
52
Gliptins
Sitagliptin, Linagliptin, Saxagliptin, Alogliptin
Inhibit DPP-4, a serine protease that degrades GLP-1
Mono or combo with metformin/sulfonylureas/TZDs
53
Adverse effects of metformin
GI complications: anorexia, N/V, etc
Lactic acidosis, esp w/ hypoxia, renal and hepatic insufficiency
Contraindicated in conditions predisposing to tissue hypoxia (HF, COPD, renal failure, alcoholism, etc)
54
Indications for Propothiouracil (PTU)
Patients w/ Graves, toxic multi-nodular goiter, methimazole intolerance, surgery or rads not happening
Ameliorates hyperthyroidism sx
Preps for thyroidectomy
Used in rad I therapy w/ methimazole intolerance
55
Main function of the parathyroid
```
Calcium homeostasis via PTH, affecting kidney:
Ca resorption (blocks Phos resorption), activates vit D
```
56
DKA vs HHS
DKA pH is below 7.3, HHS is above
DKA HCO3- is below 18, HHS is above
DKA osmolality is below 320, HHS is above
HHS hyperglycemia is above 600, DKA is above 250
57
What stimulates the release of endogenous incretins?
Oral glucose, activated by DPP-4
| The two ones are GLP-1 and GIP
58
Thyroid acropachy
In severe cases of Thyroid dermopathy (pretibial myxedema, non-pitting edema or plaques)
Soft tissue swelling, clubbing of fingers and toes, periosteal reaction of bones of hands and feet
59
Partial deficiency of 21-hydroxylase
```
Simple virilization (without salt wasting)
Nonclassic / late onset
Precocious puberty, acne, hirsutism at puberty
```
60
MODY
Looks like DMII but happens in youth
Increased blood insulin, no Abs, nonketotic
Usually from Glucokinase LOF
61
Clinical use for regular insulin
Basal maintenance
Overnight coverage
Post-prandial hyperglycemia (inject 45 min prior)
IV when urgent
62
Most common cause of death in diabetics
MI
| also at increased risk of stroke, MI, leg gangrene
63
Tigger CaSR mutation
GOF, Thinks there's plenty of Ca when there isn't
Turns off PTH (hypocalcemia)
increases renal excretion (hypercalciuria)
AD HypoPTH (hypercalciruic hypocalcemia)
64
HAGMA differential
Methanol, Uremia, DKA!, Paraldehyde, Isopropyl alcohol, Lactic acidosis, ethylene glycol, salicylates
65
Zollinger Ellison Syndrome
caused by G cell gastrinoma
Islet cell tumor + Gastric acid hyper secretion + Peptic ulceration
Do not respond to clinical diagnosis
66
Non-neoplastic causes of hyper-prolactinemia
Pregnancy, nipple stimulation, Renal Failure, Hypothyroid
Loss of DA: Lactotroph hyperplasia (neuron damage, drugs like Verapamil, Metoclopramide, antipsychotics or antidepressants with blockade of DA recs)
67
Incretin MOA
GI hormones that decrease blood glucose
Activate GLP-1 receptor or boost it
Synthesized by L-cells
Promote b-cell proliferation, insulin gene expression, glucose-dependent insulin secretion
Inhibit Glucagon secretion
Inhibits gastric emptying (causing satiety)
Short half life, not an effective drug
68
How do thiazolidinediones cause osteoporosis
Uses PPARy to direct mesenchymal stem cells away from osteoblast/Runx2 path and toward C/EBPs/Marrow adipocyte pathway
69
Where are peptic ulcers most oftenly found?
Duodenum or stomach
| Can perforate and cause free air in abdomen
70
Drugs that impair levothyroxine absorption
Antacids, Iron, Sucralfate (anti-ulcer), Cholestyramine!, orlistat, PPIs
71
Treatment of hyperthyroidism
Tx Sx w/ b-Blockers
| Tx Dz w/ high dose iodide (Wolff-Chaikoff effect), thionamide, radio iodine ablation, surgery
72
Transcription factors associated with pituitary adenomas
Most functional are associated with PIT-1
| Exception: corticotroph adenoma, TPIT associated
73
Retinal findings of diabetes
Cotton-Wool spots
VEGF-caused neovascularizations
Cataracts, glaucoma
74
Rugger Jersey Sign
Lots of space between vertebral discs
Renal Osteodystrophy
Dissecting osteitis in hyperparathyroidism
75
Follicular Adenoma of the thyroid
Discrete clonal population of follicular cells with "thyroid autonomy"
Benign, but make sure the capsule is intact (not invaded) and there's no nuclear features of papillary CA
76
Conn's Syndrome
Primary hyperaldosteronism
HTN (refractory/adrenal mass/young/severe)
Hypokalemia
Hypomagnesemia
77
Pramlintide
Amylin analog, likely at CNS receptors
Rapid onset, 3 hours duration, 20 min peak
DMI, DMII pts who take mealtime insulin
Injected SQ before meals as insulin adjunct
78
NPH MOA
```
Complex of protamine with zinc insulin
Basal maintenance / overnight. Not used much.
Onset 1-2 hours
Duration 10-12 hours
Peaks in 4-12 hours
```
79
Insulin requirements in nephropathy has gastropathy
Gastropathy: pacemaker dysfunction makes absorption and insulin need variable
Nephropathy: if they're dysfunctional, they don't clear insulin, so the requirement goes down
80
HLA typing of DMI
DR/DQ on Chr 6
81
Clinical use of thiazolidinediones
DMII, delays its progression
| No hypoglycemia when used alone
82
Craniopharyngeoma
Kids: adamantinomatous, growth retardation from hypopituitarism
Adults: papillary, increased intracranial P or hypopituitarism
83
TRH function / cascade
```
Thyrotropin releasing hormone
From hypothalamus when BMR falls
Triggers TSH release from hypophysis
Stimulates Thyroid to release TH (3 and 4)
MBP increases and suppresses further TRH
```
84
Regular insulin MOA
Unmodified zinc insulin crystals
Onset 0.5-1 hour
lasts 10 hours
Peaks in 3-5 hours
85
Growth velocities by age groups
below 4: at least 7cm/year
4-6: at least 6cm/year
6+: 5cm/year!! (2 inches)
86
Thyroid storm presentation
Extreme and abrupt episode of potentially life threatening thyrotoxicosis
87
Identify an aldosterone secreting adenoma
Spironolactone bodies
| Small, young pts, much ischemic heart dz
88
Nelson Syndrome
A Cushing's patient gets their adrenals removed, so then they get an enlarged pituitary (trying to compensate) and adenomas
89
Amylin analog MOA
OG is pancreatic and synth by b-cells
| Enhances action of insulin via inhibiting glucagon synth, decreased gastric emptying, causing satiety
90
Adverse effects of thiazolidinediones
Weight gain
Edema: increase vascular permeability, ENaC (increased Na and H2O reabsorption in collecting duct)
Worsens HF b/c water retention
Osteoporosis: Direct MSCs to adipocyte diff'n, suppress diff'n of MSCs into osteoblasts
91
Thiazolindinediones
Pioglitazone and rosiglitazone
PPARy ligands (nuclear receptor in fat, muscle liver, endothelium)
Increase GLUT4 in skeletal m. and fat, IRS1/2/PI3K
Decreased PEPCK, NF-kB, AP-1
92
Thioamide medications (3)
Propylthiouracil (PTU)
Methimazole
Carbimazole (converted to methimazole, 10x more potent)
93
Thioamide MOA
Blocks iodide organification
94
Eeyore CaSR mutations
LOF, thinks there isn't enough Ca when there is
Turns on PTH (hypercalcemia)
Reduces renal excretion (hypocalciurea)
Familial Hypocalciuric Hypercalcemia
95
Criteria for puberty being precocious
Full activation of HPG axis: girls at 8 years old, boys at 9
96
Adverse effects of supplemental insulin
Lipodystrophy (fat hypertrophy: switch up injection site)
Resistance (via IgG abs to insulin)
Allergic Rxn
Hypokalemia
Hypoglycemia (from missed meal, exercise, OD)
97
Subacute lymphocytic thyroiditis
Transient period of thyroid hormone irregularities
Hypo- (sometimes hyper-)thyroidism
Goiter
Ex. Post-partum thyroiditis, can progress to permanent hypothyroidism
98
Clinical uses of a-glycosidase inhibitors
DMII as mono therapy or combo
Oral at mealtime
Doesn't cause hypoglycemia when used alone
Dont cause weight gain
99
Osteitis Fibrosis Cystica (von Recklinghausen's dz)
Starts as Brown Tumor
| Osteoclast-driven bone destruction, small fractures, hemorrhage and reactive tissue
100
Sx of diffuse, non-toxic Goiters
Often euthyroid, sx due to mass effect: dysphagia, hoarseness, stridor, SVC syndrome
101
Sx of primary acute adrenocortical insufficiency
Adrenal crisis: rapid withdrawl of steroids
Massive adrenal hemorrhage (Waterhouse-Friderichsen)
Stress, infection, trauma, burns
102
Autoimmune polyendocrine syndrome 1
AIRE mutation
Adrenalitis, parathyroiditis, hypogonadism, pernicious anemia, mucocutaneous candidiasis (anti IL-17 and 22 Abs), Ectodermal dystrophy (fucked nails and teeth)
APECED
103
familial mutations associated with pituitary adenomas
AIP (FIPA): Somatotrophic, PAP/pituitary adenoma predisposition
104
Guidelines for DMII monitoring
Quartlerly A1c, Glucose monitoring review, foot check
| Annual eye exam, micro albumen:creatinine, monofilament testing
105
Anterior hypopituitarism
No Growth hormone, gonadotropins, TSH, Adrenocorticotrophic hormone, prolactin
106
Albright's hereditary osteodystrophy
Short stature, fingers, toes, obesity
Dental abnormalities, subQ ossification, cataracts
sometimes seizures and tetany
107
Hormone levels found in primary hypothyroidism
Increased TSH, decreased FT4
108
Most telling sign of parathyroid carcinoma
Elevated PTH that doesn't go down after surgery (mets)
109
General adrenal medulla physiology
Made of chromatin cells from NCC
| Do epi and norepinephrine from sympathetic control
110
Sulfonylurea MOA
K(atp) channel blocker
Bind to SUR1 sulfonylurea receptor
Blocking K+ current through Kir6.2 inwardly rectifying K channel
111
Pramlintide Adverse effects
N/V, vomiting, diarrhea, anorexia
Severe hypoglycemia if used w/ insulin
Enlaces anticholinergics on GI (constipation)
112
SIADH
```
Mental status changes, weakness, seizures
From small cell lung CA, Brain injury, Drugs (SSRIs)
Inappropriate thirst (unlike DI where you actually need water)
```
113
Therapeutic options for follicular carcinoma of the thyroid
Surgery, radioactive iodine
| Refractory: Chemo, TK inhibitors
114
Mechanisms of Hypercalcemia in malignancy
Humoral Hypercalcemia of Malignancy: PTHrP (PTH analog, squamous carcinomas), Vit D mediated (lymphomas)
Local Osteolytic Hypercalcemia: release of Ca (osteoclastic bone resorption, breast CA, myeloma)
115
Treatment for Somatotroph pituitary adenoma
Somatostatin analogs or GH antagonists or surgery
116
Hormone levels found in TSH producing tumor
Increased TSH, Increased FT4
117
NKHS treatment
Regular insulin 5-10 units IV bolus
3-7 units continuous infusion (transition when eating)
Monitor and replace K just like in DKA
118
General adrenal medulla physiology
Made of chromaffin cells from NCC
| Do epi and norepinephrine from sympathetic control
119
Types of Pituitary adenoma cells
Lactotroph (prolactin), Somatotroph (growth hormone), Corticotroph (ACTH), Thyrotroph (TSH), Gonadotroph (LH/FSH)
120
MEN2b
Mucosal neuromas
Marfanoid body habitus
PHeochromocytoma
Medullary thyroid CA (RET oncogene)
121
How are thyroid hormones made?
Tg (thyroglobulin) synthesized and stored in colloid
Iodide is transported into cell, incorporated into Tg
Tg endocytose and cleaved to released T3 and T4
122
Pharmacokinetics of thiazolindinediones
```
Delayed onset (1-3 months), persist weeks-months
Metabolized by the liver: half life reduced by CYP inducers (rifampin) and prolonged by CYP inhibitors (gemfibrosil)
```
123
CaSR
Calcium sensing receptor of parathyroid gland that regulates PTH
124
Sulfonylurea adverse effects
Hypoglycemia, weight gain, secondary failure (patients who respond initially later cease to respond to sulfonylureas and develop unacceptable hyperglycemia)
125
How to diagnose pheochromoctoma
Urine and plasma metanephrines
126
Dexamethasone Suppression test
Cortisol level suppressed after high dose = Cushing's
Corticotropin suppressed = adrenal tumor/hyperplasia
No suppression at all = ectopic corticotropin source
127
Best practices for evaluating premature baby growth
Adjust for height and weight for first 2 years
| Plot gestational, not chronological age for first 2 years
128
Use insulin to manage severe hyperkalemia
Insulin + glucose + Furosemide
Glucose prevents hypoglycemic shock
Insulin activates Na/K-ATPase shifting K+ into cells
Effect is transient, so eliminate the K w/ Loop diuretics
129
Clinical findings of pituitary lesions stemming from mass effect
Papilledema, bilateral temporal hemiano ia
Pituitary Apoplexy (hemorrhage into adenoma)
Underproduction of hormones (except prolactin!!)
HA, N/V, HTN, bradycardia, shallow breathing
130
Liraglutide
GLP-1 analog with 97% homology
Lipid modified: rapidly absorbed but binds to albumin
Half life is 11-15 hours
131
Histology of craniopharyngiomas
From rathke's pouch remnants
Squamous epithelium
"wet" keratin
Calcified cyst
132
Initial monitoring of DKA
Blood glucose at least hourly
Electrolytes q2-4h
Clinical status at least hourly
133
Insulin metabolic pathways
Activates MAP kinase (cell growth, etc)
| Activates PI-3K (synthesis/survival and GLUT4)
134
Estimate the height a child will reach
Height at age 2 x2
Mid-parental: Boys: [(dad + mom) +5] 2
girls: same but minus 5. This is all in inches, btw
135
Etiology of DMI
Failure of T self-tolerance against b-cells
| MHCII susceptibility on HLA DR/DQ Chr6p21
136
Hyperthyroidisms
Primary (most common): graves, hyperfunctioning multi nodular goiter, hyperfunctioning thyroid adenoma
Secondary hyperthyroidism from pituitary adenoma
Distinguish: primary has Low TSH, secondary is High
137
Secondary Hyperparathyroidism
Hypocalcemia from renal failure, gastric bypass, vit D def, pseudo-hypoPTH
Causes increased parathyroid volume adaptively
138
Growth hormone deficiency findings in neonates
Midline defects, microcephalus, hypoglycemia
| GH not relevant for growth during first year of life
139
First and second gen sulfonylureas and non-sulfonylureas (meglitinides)
1: Chlorpropamide, Tolbutamide, Tolazamide
2: Glipizide, Glyburide, Glimepriide
Non: Nateglinde, Repaglinide
140
Premature Thelarche
Palpable glandular tissue in girls below 2
| Increased over 4-6 mo period
141
Fluid replacement in NKHS
2-3 liters NS over first 1-3 hours
Fluid deficit 8-10L (reverses in 24-48 hours w/ 0.5 NS)
Glucose reaches 250 switch to d5halfNS 100-200qh
142
Findings indicative of precocious puberty
Girls: progressive breast development,
Boys: testicular and penile enlargement
Both: crossing major percentile line upward on linear growth chart
143
Primary vs secondary adrenocortical insufficiency
1: loss of cortical cells, hormonogenesis defect
2: HPA suppression by extra-adrenal steroid source
144
Distinguish PTH vs VIt D issue
PTH: Ca and PO4 go in opposite directions
| Vit D: they go in the same direction
145
Genetics of Follicular carcinoma of the thyroid
PAX8-PPARG (less than 10% are positive)
146
Adverse effects of a-glycosidase inhibitors
Malabsorption, flatulence, diarrhea, abdominal bloating
| hypoglycemia when combo'd w insulin/secretagogues
147
Goitrogens
Diffuse, non-toxic goiters
Cassava root (thiocyanate)
Brassicaceae (broccoli, cauliflower, cabbage, radish)
148
Follicular variant of papillary thyroid carcinoma
Follicular architecture with nuclear features of papillary
| More have RAS mutations (like follicular CA or Adenoma)
149
Findings of complete 21-hydroxylase deficiency
Salt Wasting: no mineralocorticoids or cortisol
Hyponatremia, Hyperkalemia, HPTN
Female virilization (at birth)
Long term HPTN
Adrenogenital syndrome (cliteromegaly, fused labia)
150
Why does chronic adrenal insufficiency cause skin hyperpigmentation?
Corticotropin releasing hormone tries to compensate by stimulating all this POMC to get it converted to ACTH but also MSH!! (melanocyte stimulating hormones)
151
Findings indicative of premature adrenarche
Increased DHEA/-S
Appearance of pubic and axillary hair, odor, acne
Normal growth and genitalia
152
Gliflozins
Inhibit SGLT2 glucose reabsorber in PCT
Canagliflozin, Dapagliflozin, Empagliflozin
Turns complete glucose reabsorption to just partial
153
Genetics of follicular neoplasms of the thyroid
RAS and PTEN
154
de Quervian's thyroiditis
Granulomatous - painful, maybe viral
Sometimes lumped in with subacute thyroiditis
Hypo- or Hyperthyroiditis
155
Hormone levels found in Central hypothyroidism
Decreased TSH, Decreased FT4
156
Hypercalcemia on EKG
Shortened QT interval
157
Genetics of anaplastic carcinoma
TP53
158
24 hour urine collection in diabetic patients for protein and creatinine clearance
Need serum creatinine at the same time to determine clearance
Its difficult to save all urine
159
Presentation of DMI in a baby
Polyuria, Polydipsia, lethagy, weight loss, extreme hunger
160
Cells of the endocrine pancreas
D1: Secretes VIP (vasoactive intestinal polypeptide)
Delta: somatostatin
PP: pancreatic polypeptide
161
DEXA scan scoring
Normal is -1 or higher
Osteopenia is -1 to -2.5
Osteoporosis is less than -2.5 (severe w/ fracture)
162
Microalbumen:Creatine
Random urine sample
More accurate than micro albumin alone because it corrects for variations from [urine]
Microalbuminuria = 30-300mg
163
Most additive risk for vascular disease
SMOKING
164
Myxedema
Hypothyroidism in the adult/older child
Mental and physical sluggishness
Weight gain, cold intolerance, cardiac effect (lower output, hypercholesterolemia)
165
Cushing's syndrome vs disease
Disease is from a pituitary corticotroph adenoma
Syndrome can come from many other things
Both have abdominal striae, thin skin, hirsutism, etc
166
Initial insulin administration for DKA
10-20 units IV, the 5-10 per hour continuous IV
| Increase if no response in 1-2 hours
167
Medullary thyroid carcinoma
Sporadic: Most common, univocal, aggressive, 50y.o.
Familial: 100% 15-year survival, multifocal, 43 y.o.
Ass'd w/ RET oncogene on chr 10
From C Cells (Calcitonin)
Polygonal-to-spindle shaped cells forming nests in trabeculae
Amyloid!
168
Pharmacokinetics of metformin
Half life 1.5-3 hours
| Not bound to plasma proteins, not metabolized, excreted unchanged by kidneys
169
Graves disease
Hyperthyroidism with gland enlargement
Infiltrative opthalmopathy (can have lines on eyes)
Pretibial Myxedema
170
Acute vs chronic adrenal insufficiency sx
Acute: HPTN, abdominal pain, N/V, Hypo-N/Glycemia
Chronic: malaise, joint pain, hyperpigmentation
171
Riedel thyroiditis
Fibrosing, extends from thyroid to adjacent tissue
Feels like cement
Lots of lymphocytes and plasma cells
IgG4-related, EUTHYROID
172
Why taper steroids tp treat adrenocortical insufficiency
Can cause adrenal atrophy
173
Criteria for delayed bone age
Two SD below chronologic age, assessed by ossification of epiphyseal centers
174
Propothiouracil MOA
Inhibits synthesis of thyroid hormones in hyper-
Inhibits thyroxine to triiodothyronine conversion peripherally
Does not inactivate pre-existing T3/4!
Does not interfere with given hormones!
175
Histology of Hashimoto thyroiditis
Atrophic follicle cells with eosinophilic change (Hurthle cell metaplasia)
176
Treatment for lactotroph adenoma
DA agonists (bromocriptine, Cabergoline), surgery
177
What Abs would you expect to find in DMI?
Islet auto-abs: Anti-insulin, GAD, ICA512
178
How to attenuate the glucose-lowering effects of sulfonylureas
Inhibit insulin secretion: b-blockers, CCBs
| Induce hepatic CYPs: Phenytoin, griseofulvin, rifampin
179
Gonadotrophic pituitary adenoma presentation
Minimal function, often silent maybe with only mass effect
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Advantages of metformin
really good, doesn't cause hypoglycemia or weight gain, oral, alone or in combo, decreased risk of macro- and microvascular complications in diabetic pts
181
DKA treatment goals
Increase rate of glucose utilization (150-250)
Reverse ketonemia and acidosis
correct depletion of water and electrolytes
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Diabetic Gastropathy
Autonomic neuropathy where gastric pacemaker becomes too variable. Nutrient and glucose requirements become extremely variable too
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Presentation of hyperthyroidism
Lid lag, exophthalmos
Bruits over thyroid
Goiter, nodules, Tremor, warm skin, Gyno, weakness
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MODY
Looks like DMII but happens in youth
Increased blood insulin, no Abs, nonketotic
Usually from Glucokinase LOF
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Side effects of gliflozins
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Osmotic diuresis
Weight loss
Reduced BP
Reduced plasma Uric acid
Dont cause hypoglycemia when used alone
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Bilateral cortical hyperplasia
Expected in ACTH dependent Cushing syndrome (secondary)
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Follicular Carcinoma of the thyroid
Less common unless there's iodide deficiency
PAX8/PPARG mut are characteristic (RAS less so)
Invaded (mushroom) capsule
Angioinvasion
Still considered differentiated thyroid CA
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Clinical presentation of apathetic hyperthyroidism
older adults with masked sx
unexplained weight loss
Cardiovascular disease
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Types of Insulin by speed
Rapid: Aspart, Lispro, Glulisine
Short: Regular
Intermediate: NPH
Long: Detemir, Glargine
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Exenatide
Recombinant exendin-4 w/GLP-1 activity
| Modified Gila monster saliva, less susceptible to hydrolysis by DPP-4
191
VIPoma
D1 cells, intestinal fluid secretion
WDHA syndrome: watery diarrhea, hypokalemia, achlorhydria
20% have flushing as well
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Endogenous factors of insulin secretion regulation
Glucose and other energy substrates
GPCR-Gs ligands: b2-AR and GLP-1 agonists (incretins)
GPCR-Gi ligands: somatostatin, a2-AR agonists
193
Etiology of secondary hyperaldosteronism
RAAS: diuretics, bad renal perfusion, arterial hypovolemia, pregnancy, renin-tumors
194
What pediatric patients do you send for referral?
Hight below 3rd or above 95%
Above 5cm/2in variance from mid-parental height
Bone age fast or slowed by above 2 SD
Abnormal growth velocity, dysmorphic features
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Somatic mutations associated with pituitary adenomas
USP8: corticotrophic, up regulates EGFR
GNAS: somatotroph. Makes a-subunit of Gs lose GTPase activity, proliferation cascade is constantly active
196
Adverse effects of Gliflozins
HPTN, hypovolemia
Hypovolemic pts: ortho HPTN, dizziness, syncope
Genital and UTI
Hypoglycemia if combo'd w/ insulin or secretagogues
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Detemir MOA
Lys29 in b-chain is myristoylated (lipid: rapidly absorbed into blood but binds strongly to albumin)
Peaks in 3-9 hours
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Pheochromocytoma presentation and distribution
Profound HTN from adrenal tumor
Triad of HA, palpitations, Diaphoresis
10% are extra-adrenal, bilateral, pediatric, malignant, non-HTN associated
25% are familial
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C-peptide
Co-product of insulin creation
| Marks endogenous insulin (can differentiate from pharmaceutical)
200
Histologic difference between parathyroid hyperplasia and parathyroid adenoma
Hyperplasia does not have that normal rim of parathyroid tissue
One gland affected is adenoma, all means hyperplasia
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Rathke's cleft cyst
During development, neck pf pouch constricted by mesoderm and pinches it off.
Can expand and compress normal pituitary
Can rupture and cause inflammation of pituitary, meningitis
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What do incretin mimetic do in addition to long-acting GLP-1 receptor activation?
DPP-4 inhibition (usually inactivates GLP-1)
203
What are the two long-acting GLP-1 receptor agonists?
Exenatide and Liraglutide
204
Etiologies of non-ketotic hyperosmolar state
Insulin deficiency, inadequate fluid intake, osmotic diuresis from hyperglycemia
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Pineal gland function
Produces melatonin, made from photoreceptor containing neural tissue
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Insulinoma
Small tumors causing hypoglycemia, often have amyloid. Dx via C peptide
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Possible damage done during thyroid surgery
Recurrent laryngeal nerve
| Damage to parathyroid glands
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K-I indications
Treats hyperthyroidism, I deficiency, combo'd w/ other anti-thyroids to prep for surgical removal
Protects thyroid from radiation, shrinks it to reduce hormones (spares Cardio stuff)
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Methimazole MOA
Inhibits thyroperoxidase (normally catalyzes T3/4 synth)
Taken before thyroid surgery to lower hormone levels
Minimizes effects of thyroid manipulation
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Hashimoto Thyroiditis
Abs against thyroglobulin and thyroid peroxidase (TPO)
Diffuse, painless enlargement
Hypothyroid (except in hashitoxicosis)
211
Growth hormone deficiency in children
Decreasing growth velocity
Low IGF-1 and IGFBP-3
Low GH levels during stimulation test (Insulin, Argenine, Clonidine)
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a-Glycosidase inhibitors
Acarbose and Miglitol
Competitive inhibitors of GI epithelium enzymes
Lower postprandial hyperglycemia for insulin-sparing
213
Diffuse sclerosino variant of papillary thyroid carcinoma
Younger patients, more mets to lung, brain, bone, liver
Shorter periods of disease-free survival
Mortality comparable to those of conventional PTCs (93% survival at 10 years)
214
Manage 21-hydroxylase deficiency
Glucocorticoids (does negative feedback for ACTH suppression, no more androgen over-stim)
215
PTH is high but Ca is low
Secondary Parathyroid hyperplasia, typically 4-gland hyperplasia
216
Fasting plasma glucose, two-hour glucose, and A1c values that diagnose DM
FPG 126+
2-hour 200+ during a 75g Oral glucose tolerance test
A1c 6.5+
217
How does DKA come about?
Insulin Deficiency causes FFA release, making ketones
Shock, dehydration release epinephrine
Epi means body cant use glucose, accumulates
Glucagon promotes gluconeogenesis
Kidneys dump glucose, ketones: osmotic diuresis
218
Complications of pheochromocytoma
Chronic causes cardiomyopathy
219
Lactotrophic pituitary adenoma presentation
F: Amenorrhea, Galactorrhea, low libido, infertility, mass
M: Decreased libido, sperm count, mass effect
220
Hypocalcemia findings
Behavioral disturbances, stupor, cramps, convulsions
Trosseau, chovstek signs
Prolonged QT
221
Anaplastic Carcinoma of the thyroid
Uncommon, in elderly, highly aggressive
Present with mass effect, die within year of invasion
Microscopy shows papillary CA w/ high grade tumor
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Definition of short stature
Hight 2 SD below mean for age and sex (below 3rd%)
| Height more than 2 SD below pid-parental height
223
What ketones accumulate in DKA?
Acetoacetic acid
| Beta-hydroxybutyrate
224
Precursors to DKA
Pneumonia, UTIs
| Non-compliance is the most common cause (DMI)
225
How would you identify nephropathy in a patient with DMII?
Spot (random) urine sample: urine dipstick not sensitive to proteinuria below 300mg. Most common protein is Albumen
226
Ddx for pediatric tall stature
Beckwith-Wiedemann (IGF-2, big head)
Homocystinuria (methionine metabolism error)
Klinefelter (47XXY)
Marfan (Fibrillin-1 mut, Dx by Ghent Nosology)
227
Posterior pituitary hormones
ADH (deficient = DI, excess = SIADH) and Oxytocin
228
Lactotroph adenoma histology
Stromal hyalinization with Psamomma bodies
| Dense calcification
229
Findings of diabetic nephropathy
Glomerular sclerosis: thickening of BM, disruption of protein cross-linkages that make barrier, causes large molecule (protein) leak (Kimmelstiel-Wilson Disease)
Renal vascular lesions (arteriolosclerosis)
Pyelonephritis
230
Differentiate corticotroph pituitary adenomas vs ACTH-secreting tumors and adrenal tumors
Pituitary Coricotroph: ACTH supression w/ high dose dexamethasone suppression test.
Ectopic corticotroph: Not suppressed, high serum cortisol AND corticotropin
Adrenal tumor/hyperplasia: not suppressed, high cortisol
231
Presentation of regular hyperthyroidism
Exopthalmos, Jittery, palpitations, sweating, flushing
232
When can you start intermediate or long-acting insulin in a DKA patient?
Mental status and GI issues improve
Anion gap normalized
Allow overlap time of 30-60 min
233
Adverse drug interactions of sulfonylureas
Displace from binding w plasma proteins (sulfonamides, clofibrate, salicylates, other NSAIDs)
Ethanol
Inhibiting CYP enzymes (azalea antifungals, gemfibrozil, cimetidine)
234
Progression of Hashimoto thyroiditis
Immune mediated insult, then hyperactivity and enlargement, then follicular cell exhaustion
235
When do growth spurts usually occur?
First 18 months, when more table food is introduced
| Can be catch-up or catch-down
236
Presentation of Glucagonoma
Mild diabetes
Characteristic rash: Necrolytic migratory erythema on groin, lower extremities. Progresses to shedding, bull, crusted erosions
4 D's: Diabetes, Dermatitis, Depression, DVTs
237
Drug targeting factors of insulin secretion regulation
Resting membrane potential (specifically Katp channel)
VDCC (L-type Ca channel)
GPCR-Gs / Gi / cAMP axis
238
Treatment for corticotroph pituitary adenomas
Somatostatin analogs, bromocriptine, surgery
| they can express DA / somatostatin recs
239
Sx of hypoglycemia
Confusion, seizures, coma
Sympathetics (tachycardia, palpitations, sweat, tremor)
Parasympathetics: Hunger, nausea
Tx w/ glucose or sucrose or glucagon
240
Major side effects of Methimazole
Agranulocytosis, leukopenia, thrombocytopenia, etc
Elevated Serum transaminases, jaundice, hepatitis
Be careful if they have liver disease/EtOH/hepatitis!!
241
Differentiate central vs nephrogenic DI in the clinic
Administer DDAVP
| Water better retained? Central. No? Nephrogenic
242
Types of amiodarone-induced thyrotoxicosis
1: underlying thyroid pathology (like graves)
2: Amiodarone-caused, release pre-formed thyroid hormones into the circulation
243
Amiodarone
Commonly Rx for arrhythmia
Can cause Type II amiodarine induced thyrotoxicosis (actual thyroid tissue destruction)
Repeat TSH, free T3/4 levels q6-12mo
Check for emerging sx of hyperthyroidism
244
Congenital Hypoparathyroidism causes
DiGeorge: defects in 3rd/4th pharyngeal pouches, parathyroid glands maybe absent or underdeveloped
CASR germline mutations: familial hypocalcemic hypercalciuria (hyperactive Ca-sensing receptors)
Familial isolated Hypoparathyroidism: Precursor PTH cant get all the way to functional PTH
245
Somatotrophin pituitary adenoma
Gigantism (before epiphyseal closes), Acromegaly (after)
Serum levels of IGF-1 elevated? oral glucose tolerance test for GH response
Enlarged viscera, fatal CV problems, Joint pain
246
Genetics of papillary carcinoma of the thyroid
RET/PTC rearrangements: constitutive TK activity
| BRAF GOFs: MAP kinase signaling
247
Medullary thyroid carcinoma
Sporadic: Most common, univocal, aggressive, 50y.o.
Familial: 100% 15-year survival, multifocal, 43 y.o.
Ass'd w/ RET oncogene on chr 10
248
Adrenocortical insufficiency gives you a lack of mineralocorticoids. What would this look like?
Hyper-K, hypo-Na
249
Most common auto-ab in grave's
Thyroid stimulating hormone receptro antibody
250
Differentiate adenomatous vs carcinomatous adrenal cortical neoplasms
both are incidental, functional
| Carcinomas compress/invade and virilize
251
What does A1c measure?
Glucose binding to RBCs
Gives 3-4 month average of blood sugars
Less than 6.5 is good
252
Most common cause of Cushing sydnrome
Iatrogenic: glucocorticoid administration
253
Pleomorphic spindle cells
Anaplastic Thyroid CA
