Endocrinology - MIDTERM Flashcards
T/F Routine thyroid function testing is recommended in asymptomatic patients
False - not recommended (outside of newborn screening)
What medications put a person at risk for thyroid disease?
Lithium
Amiodarone
Risk factors for thyroid disease? What age of women vs men?
- men: age ≥ 60
- women: age ≥ 50
- personal history or strong family history of thyroid disease;
- diagnosis of other autoimmune diseases (T1DM, celiac)
- past history of neck irradiation;
- previous thyroidectomy or radioactive iodine ablation;
- drug therapies such as lithium and amiodarone;
- dietary factors (iodine excess and iodine deficiency in patients from developing countries); or
- certain chromosomal or genetic disorders (e.g., Turner syndrome,3
Down syndrome4
and mitochondrial disease5
-postpartum period
T/F Goitre can occur in either hypo or hyperthyroidism
True
S&S of hypothroidism
- Depression
- Decreased mental function
- ataxia
- Physical tiredness
- Paresthesia
- Hypokinesis
- Hyporeflexia
- Weight gain
- Coarse, dry skin
- Coarseness or loss of hair, inability of hair to hold a curl,
hair loss at eyebrows, and reduced growth of hair.
-reduced growth of nails - Periorbital edema
- Hoarseness
Bradycardia - Isolated diastolic hypertension
Goitre
Diminished sweating - Cold intolerance
Constipation
What is the effect of hypothroidism vs hyperthroidism on menstruation?
Hypo - menorrhagia (heavy bleeding), irregular periods
Hyper - amenorrhea/oligomenorrhea
T/F A TSH value within normal range excludes majority of cases of primary thyroid disorders
True
When do we do an US of the thyroid?
thyroid ultrasound scan is not routinely recommended in patients with abnormal thyroid function tests, unless there
is a palpable abnormality of the thyroid gland
What TSH and fT4 levels would you expect to see in hypothroidism?
High TSH
Low fT4
What TSH and fT4 in hyperthyroidism?
Low TSH
High fT4
Your patient is diagnosed with hypothyroidism and started on medication. How long should you wait before rechecking TSH?
6 weeks (rxfiles says 6-8 weeks)
- also applies for dosage changes
(consider more frequent if pt clinical status changes)
Also need to retest if weight change >20lbs
How does subclinical hypothyroidism look?
Typically asymptomatic or very nonspecific symptoms
Elevated TSH (usually <10mU/L). fT4 normal
Overtreatment with levothyroxine can cause?
atrial fibrillation (more commonly in the elderly) and bone loss in postmenopausal women
+ all other symptoms of hyperthroid
Once TSH has normalized with treatment (euthyroid), it should be checked ____ unless a new indication arises. This confirms adequacy
of treatment dose and compliance with therapy.
Annually
Does the time of day matter when taking thyroid levels?
Yes, TSH levels in the same individual can vary by 50% when measured at different
times of day, with lowest values in the late afternoon and highest values at midnight.
(RxFiles says draw blood in AM)
In individuals with subclinical
hypothyroidism, TSH values can vary by up to 40% even when measured at the same time on different days without indicating
a change in thyroid function. As long as TSH remains within the reference interval, changes over time are not important.
How often do patients on lithium and amiodarone need to have their thyroid function checked?
Lithium: q 6 months
Amio: q 3-6 months
Who is more likely to experience subclinical hypothyroidism?
Women
Advanced age
When do we treat subclinical hypothyroidism?
According to BC guidelines:
is recommended when TSH rises above 10 mU/L
Treatment can be
considered when TSH is between the upper limit of the reference interval but ≤10 mU/L and any of the following are present:
- symptoms suggestive of hypothyroidism
- elevated TPO antibodies
- evidence of atherosclerotic cardiovascular disease, heart failure, or associated risk factors for these diseases; or
- pregnancy
(Rxfiles also says young adults <30yrs)
How often do we monitor patients with subclinical hypothroid who aren’t getting treated?
q 6-12 months or sooner if change in clinical situation
Is hypothyroidism generally considered permanent?
Yes, will usually require lifelong treatment
Most common cause of hypothyroidism?
Hashimotos thyroiditis (autoimmune)
What is a normal TSH level?
0.45 to 4.5mIU/L
TSH Level in hypothyroidism = _____
> 10
TSH levels in subclinical hypothyroidism typically:
4-10 (guidelines vary)
Starting does of levothyroxine? (differentiate healthy young vs older adult vs hypothyroidism)
Young, healthy: use full replacement dose of
1.6-1.7 mcg/kg/d
> 50 years old, or CVD: start at 12.5-25mcg daily ↑ q4-8 wk. If ↑ CVD symptoms, decrease dose
Subclinical: if treating, start at 25-50mcg daily.
What is PCOS? What does PCOS cause?
Dysfunction of the hypothalamic pituitary ovarian axis. Is a syndrome of coexisting conditions:
- excess insulin & androgens
- irregular/ anovulatory menstrual cycle (possible infertility)
- polycystic ovaries
… in people with female sex organs
Risk factors for PCOS
- Irregular ovulation
- Obesity/insulin resistance
- Diabetes (type 1 and 2)
- Hx of premature adenarche (early sexual maturation)
- 1st degree relative with PCOS
- Antiseizure meds (valproate)
When does PCOS typically present?
Clinical manifestations of PCOS usually appear within 2 years of puberty.
May appear after a period of normal menstrual function and pregnancy.
S&S of PCOS
- Hirsutism (dark hair on face, back, etc)
- Alopecia (male pattern)
- Acne (can be severe)
- Hyperhydrosis (excess sweating)
- Acanthosis nigricans.
- Obesity (41%)
- Menstrual disturbances/ Infertility
- Increased insulin
- Increased androgen (testosterone, androstenedione)
Lots of other hormones out of wack (LH, prolactin, DHEA)
20% asymptomatic
What are the possible late sequelae of PCOS (complications)?
Dyslipidemia
DM
CVD, HTN
Endometrial hyperplasia & carcinoma
Criteria for diagnosis of PCOS?
Are differing criteria but Rotterdam criteria from 2003 says must have 2 of 3 of the following:
1) Hyperandrogenism
2) Oligomenorrhea
3) Polycystic ovaries
Another from 2009 states must have hyperandrogenism and either oligomenorrhea or polycystic ovaries
Other tests that may be helpful but are not necessary for diagnosis include measurement of LH and follicle-stimulating hormone (FSH) levels to determine a serum ratio of LH/FSH
Treatment of PCOS (complex but basic idea…)
Depends on whether pt wants to get pregnant or not…
Seems like generally you’re just treating each of the symptoms.
Aggressive lifestyle modification focused on increased physical activity and weight loss is mainstay treatment (weight loss may resolve infertility)
Oral contraceptive pills (OCPs) are the most commonly used treatment for endometrial prevention and
hirsutism
Metformin is used to manage oligomenorrhoea, cause
weight loss, lower insulin levels, and induce ovulation for
women with PCOS:
Acne: topical cream, contraceptives
Spironolactone is used after a four- to six-month oral
contraceptive trial as antiandrogen therapy:
Lots of other complex things that I assume would be managed by a specialist (endo or gyn)
What is addison’s disease
Primary adrenal insufficiency resulting in glucocorticoid
and mineralocorticoid insufficiency.
Chronic form of adrenal gland destruction
What populations are morel likely to get addison’s disease
more common in women and
children
overall very rare - Approximately 40 to 60 cases per million people;
What causes addison’s?
Autoimmune dysfunction of the adrenals accounts for up to 80% of cases (mostly in developed world)
10% to 20% of cases are attributed to TB (spreads to adrenal glands)
Patho of addisons
At least 90% of the adrenal gland is destroyed (only become symptomatic once this extensive destruction)
Reduced levels of aldosterone –> RAAS system affected –> Low Na+ and High K+ , hypovolemia, metabolic acidosis
Reduced cortisol –> low blood gluc in times of stress –> fatigue, weakness
Reduced androgens –> women lose body hair and libido (men not affected because major source of androgens in testes)
Why do we see hyperpigmentation of the skin in addisons?
Pituitary becomes hyperactive to compensate for low cortisol, which results in overproduction of melanocyte stimulating hormone
Where is this hyperpigmentation most visible?
Joints + sun exposed areas
commonly knuckles
S&S of Addison’s disease
Weakness/fatigue
Abdo pain
N/V/D
Anorexia
Weight loss
Hyperpigmentation
Hypoglycemia
Low libido
Salt craving
Muscle & joint pain
Reduced axillary/pubic hair in women
Amenorrhea
Hypotension
Anemia
ECG changes
What is an Addisonian crisis? (acute adrenal crisis)
May be brought on by stressful event (surgery, infection, injury), resulting in sudden need for aldosterone or cortisol
= Medical emergency
S&S of Addisonian crisis
sudden low back,
abdominal, or leg pain
severe vomiting or diarrhea
hypotension
loss of consciousness
Death
Diagnosis of Addisons
Adrenocorticotropic hormone stimulation test: give synthetic ACTH and then measure to see amount of cortisol produced. If low, would indicate adrenal insufficiency (but doesn’t specify if primary or secondary cause).
Need plasma ACTH level to differentiate (will be be high if primary adrenal insufficiency like Addisons)
-Anti-adrenal antibodies (not super useful)
-CT scan of adrenals - can help differentiate if metastatic disease, sarcoidosis, or TB
Treatment for Addisons
*Consult endocrinologist!
Will need hormones:
cortisol (flurocortisone and hydrocortisone) , aldosterone, androgens
- typically taken for rest of life. Otherwise have risk of addisonian crisis
**Need coaching on how to limit risk of infection & what to look for in addisonian crisis
What is Cushing’s syndrome?
= a cluster of symptoms, signs, and
biochemical abnormalities arising from glucocorticoid over-production.
-Key feature is high cortisol and loss of normal feedback control mechanisms
Cushings causes - What are the 2 main categories for etiology?
Can be caused by endogenous or exogenous cortisol (aka steroid use)
-ACTH dependant (85%)-bilateral adrenal hyperplasia and cortisol hypersecretion due to ACTH secreting pituitary adenoma (true Cushing’s disease) or ectopic ACTH secreting tumour (small cell lung ca, pancreatic islet cell, pheochromocytoma, medullary thyroid tumour)
-ACTH independent (15%)- iatrogenic (excess cortisol from long term glucocorticoid use), primary adrenocortical tumors, benign adrenal nodular hyperplasia
Basic patho of cushings
High cortisol levels =
–> severe muscle, bone and skin breakdown
–> elevated blood glucose + high insulin levels –> central obesity
–> HTN
–> inhibit gonadotropic release hormone –> mess up up ovarian and testicular fx
–> dampens inflammatory and immune response –> inc risk of infection
–> Impaired normal brain fx
Name the 1 million S&S of Cushing’s
General: Insomnia, disturbed sleep, weight gain (trunk, moon face, cervical buffalo hump), thin extremities from muscle wasting
Metabolic: intolerance, DM
Integ: weak, thin skin; easy bruising, striae (purple), ulceration, acne, acanthosis nigricans,
CVS: vasoconstriction, HTN
MSK: Osteoporosis and compression #, back pain, height reduction, kyphosis, muscle wasting
GU: mineral corticoids promote hypokalemia, sodium and water retention
Neuro/ MH: irritable, depressed, schizophrenia like symptoms, impaired cognition
Gyne: changes in sex hormones (in F= irregular periods or amenorrhea, hirsutism, acne; in M= erectile problems or changes in sex drive)
Other: suppressed immune system, susceptibility to infection
Diagnosis of Cushings
- Measure 24 hour free cortisol from 24hr urine sample
- Can also check blood and saliva tests late at night to see if normal rise and fall of cortisol levels
- Can also do dexamethasone suppression test –> should cause decrease in serum cortisol levels
- ACTH plasma levels
MRI of pituitary, CT of adrenals
Tx of cushing’s
Depends on cause
- If exogenous: Slow decrease causative meds (steroids) so doesn’t cause Addisonian crisis (as adrenals have atrophied)
- surgical excision of adenoma
- adrenal steroid inhibitors
What are the 4 kinds of diagnostic tests for DMT2? (don’t need to give specific cutoff points, just names of tests)
1) Fasting plasma glucose
2) A1c
3) 2hPG in a 75g OTGG
4) random gluc
FPG of what level is potentially diagnostic for DM?
How long is it necessary to fast?
> or equal to 7mmol/L (no caloric intake x 8 hrs)
A1C of what level is potentially diagnostic for DM?
> or equal to 6.5%
2hPG in a 75OGTT of what value is potentially diagnostic of DM?
> or equal to 11.1mmol/L
Random plasma gluc of what value is potentially diagnostic of DM?
> or equal to 11.1mmol/L
You patient’s random gluc comes back at 11.5mmol/L but they aren’t having any symptoms. You didn’t take any other of the diagnostic tests.
Can you diagnose them with diabetes?
NO,
In the absence of symptomatic hyperglycemia, if a single laboratory test result is in the diabetes range, a repeat confirmatory laboratory test (FPG, A1C, 2hPG in a 75 g OGTT) must be done on another day. It is preferable that the same test be repeated (in a timely fashion) for confirmation, but a random PG in the diabetes range in an asymptomatic individual should be confirmed with an alternate test
Your patients A1C comes back at 7% and they are having polyuria and generally don’t feel well.
Can you diagnose them with diabetes?
Yes
In the case of symptomatic hyperglycemia, the diagnosis has been made and a confirmatory test is not required before treatment is initiated
Your patient’s A1C is 7.0 and their random gluc is 11.1mmol/L. Can you diagnose DM?
Yes
If results of 2 different tests are available and both are above the diagnostic thresholds, the diagnosis of diabetes is confirmed.
Your patient’s A1C is 6.7%. They are asymptomatic. You don’t have any other lab results related to DM. What is your next step?
Need to repeat A1C on different day.
If is still elevated, can diagnose DM.
In the absence of symptomatic hyperglycemia, if a single laboratory test result is in the diabetes range, a repeat confirmatory laboratory test (FPG, A1C, 2hPG in a 75 g OGTT) must be done on another day. It is preferable that the same test be repeated (in a timely fashion) for confirmation, but a random PG in the diabetes range in an asymptomatic individual should be confirmed with an alternate test
How were the numbers for DM diagnosis determined? (Sarah emphasized this in lecture)
Cutoff points at which high risk of future retinopathy was seen in research.
Is OGTT used commonly in diagnosing DM?
How is it used in at risk individuals?
Just in pregnancy.
Otherwise not commonly used as is inconvenient.
Guidelines recommends that for individuals in the “at risk” and prediabetes categories, it is also worth considering a OGTT, especially when clinical suspicion is high due to presence of risk factors
What constitutes prediabetes in terms of A1C and FPG?
AIC 6.0 to 6.4%
FPG 6.1 - 1.9
Who gets screened for T2DM and how often?
If no risk factors and less than 40 years old, no screening indicated
Screen every 3 years if 40 or older, or at high risk using a risk calculator (but none of risk factors from next question I believe?)
Screen earlier and every 6-12 months in people with additional risk factors for diabetes (next question) or those at very high risk using risk calculator
(I find this unclear/confusing)
Name some risk factors for T2DM
Age ≥40 years
First-degree relative with type 2 diabetes
Member of high-risk population (e.g. African, Arab, Asian, Hispanic, Indigenous or South Asian descent, low socioeconomic status)
History of prediabetes
History of GDM
History of delivery of a macrosomic infant
Presence of end organ damage associated with diabetes:
Presence of vascular risk factors: smoking, abdo obesity/overweight, HTN, elevated TG or HDLs
Presence of associated diseases: pancreatitis, PCOS, acanthosis nigricans, gout, NAFL,, psychiatric disorders. HIV infection, OSA, CF
use of drugs associated with DM (see next question)
…basically everybody
What medications are associated with diabetes?
Glucocorticoids
Atypical antipsychotics
Statins
Highly active antiretroviral therapy‡
Anti-rejection drugs
Most adults with Types 1 or 2 diabetes should aim for a H1C target of?
< or equal to 7.0
If low risk of hypoglycemia and have T2DM, can aim for < or equal to 6.5 to reduce risks of retinopathy and CKD
What about A1C goals for those who are functionally dependent, have hypglycemia unawareness or limited life expectancr?
Functionally dependent*: 7.1-8.0%
Recurrent severe hypoglycemia and/or hypoglycemia unawareness: 7.1-8.5%
Limited life expectancy: 7.1-8.5%
Frail elderly and/or with dementia†
: 7.1-8.5%
At the diagnosis of T2DM, you find your patients A1C is < 1.5% above target, what do you do?
Start healthy behaviour interventions (nutritional therapy, weight management, physical activity) +/- metformin
If not wanting to start metformin right away, can give 3 months and then recheck to see if at glycemic target.
The same patient comes back in 3 months and their A1C is still not at target. What now?
If have not already started metformin, start it now.
If already on it, increase dose.
If you diagnose a patient with T2DM and their A1C is > 1.5% above target, what do you do?
Lifestyle modificatins
Start metformin as well as a second agent
If, at the time of diagnosis, your patient is symptomatic for hyperglycemia and/or has metabolic decompensation (dehydration, DKA, HHS), what do you do?
Lifestyle modifications
Start insulin with or without metformin
Your patient is on metformin and still not reaching their A1C target so you need to add an agent. They have a history of CKD (GFR 44) and HF. What are some good options?
GLP1 or SGLT2
(According to figure 2.1 in quick reference guide, SGLT2 will never be the wrong answer because is both cardio and renal protective!)
What are the main CV risk factors to consider to would point to benefits of using cardio and renal protective meds for diabetes?
Tobacco use
Dyslipidemia
HTN
When you start a GLP1, you need to stop what medications?
DPP4i
An SGLT2 is only okay to initiate if GFR is > ______?
30 ml/min
Name 3 GLP1s and 3 SGLT2s with proven cardiorenal benefit in high-risk populations (comes from Fig 2.2)
GLP1:
semaglutide
dulaglutide
liraglutide
SGLT2i
canagliflozin
dapagliflozin
empagliflozin
If a patient with diabetes has CVD (cardiac ischemia, PAD, cerebrovascular/carotid disease), what additional medications will you add?
Statin
ACEi/ARB
ASA
If you patient with DM has microvascular disease or is >55 years old with additional CV risk factors, what medications will you add?
statin
ACE/ARB
If you patient is
>(or equal to) 40
Age 30 with diabetes >15 years
What meds will you start?
Statin
(and also if this is warranted based on the lipid guidelines of course)
Which diabetes meds are highest risk for hypoglycemia?
Sulfonureas (glyburide, gliclazide) repaglinide (a meglitinaide) or insulin
Medications that end in “gliptin” are what class?
DPP4 inhibitors
T/F Giving a long acting insulin once daily has less risk of hypoglycemia than giving multiple daily doses
True - severe risk in high intensive approaches to insulin
Which antihyperglycemics are hardest on the GI system?
Metformin
GLP1
(start low go slow)
T/F Metformin has very low risk of hypoglycemia
True (is the least risk)
Are GLP1s or SGLT2s more renal protective?
SGLT2s
GLP1s and SGLT2s are high risk for hypoglycemia when given with?
Sulfonureas or insulin (which makes sense because these are already high/severe risk on their own!)
Which antihyperglycemics are beneficial for weight loss?
GLP1s = most
SGLT2 and metformin also
Which meds cause the most weight gain?
Insulin (especially high intensity) & TZDs are highest
Then sulfonureas & meglitinides
Effects on A1C of: metformin, sulfonureas, and GLP1, and meglitinides on A1C?
All are decrease by 1-1.5%
Effect of DPP4s and SGLT2s on A1C?
Both more modest effect
DPP4i’s 0.5-0.7%
SGLT2s: 0.5 - 0.8%
Effect of TZDs on A1C?
1.0%
Patient teaching to give regarding GLP1s to reduce GI upset?
What can we do with dosing to decrease SEs?
start low, titrate as per
product monograph (slower if not tolerating),
Consider HS dosing
eat smaller, more frequent &
low fat meals slowly
What is an absolute contraindication to using a GLP1?
personal/family hx medullary thyroid carcinoma;
multiple endocrine neoplasia syndrome type 2
What are the SADMANs medications?
If ill and unable to maintain fluid intake or has acute decline in renal function, should hold these meds:
Sulfonylureas
ACEIs
Diuretics
Metformin
ARBs
NSAIDs
SGLT2i
How big of an effect can diet have on A1C?
1-2%
Exercise recommendations for someone with DM?
At least 150 min per wk of moderate-vigorous aerobic exercise and at least 2 sessions per wk of resistance exercise
Metformin is contraindicated for eGFR <____? Or what other condition?
CI if eGFR <30ml/ min or hepatic failure;
dose reductions if eGFR 30-60
MOA of metformin
-Increases insulin sensitivity in liver and tissues (adipose, muscle)
-Decreases insulin production from liver
-Body uses glucose more effectively
-Activates AMP-activated protein kinase
MOA of sulfonureas?
Acts on pancreas beta cells to stimulate insulin secretion (secretagogues)
MOA of DPP4s
Incretin; increases glucose dependent insulin release, slows gastric emptying, inhibits glucagon release
MOA of GLP1s
Incretin; increases glucose dependent insulin release, decreases gastric emptying, inhibits glucagon release
-Reduces appetite
MOA of SGLT2
Reduces glucose reabsorption by kidney (pee out the sugar)
MOA of TZDs
Increases insulin sensitivity in the liver and peripheral (adipose, muscle) tissues
TZDs end in what?
“glitazones”
Rosiglitazone, Pioglitazone
Common adverse effects of SGLT2s?
-Genital mycotic infections
-UTI
-Hypotension
-Rare cases DKA
-Rare AKI
Adverse effects of sulfonylureas?
-hypoglycemia and weight gain
SE of metformin
-GI, Nausea, diarrhea (go away as ody gets used to)
-B12 deficiency
Describe treatment of mild to moderate hypoglycemia
Evidence suggests that 15 g glucose (monosaccharide) is required to produce an increase in BG of approximately 2.1 mmol/L within 20 minutes, with adequate symptom relief for most people
15 g of glucose in the form of glucose tablets
15 mL (3 teaspoons) or 3 packets of table sugar dissolved in water
5 cubes of sugar
150 mL of juice or regular soft drink
6 Life Savers™ (1 = 2.5 g of carbohydrate)
15 mL (1 tablespoon) of honey
avoid over-treatment since this can result in rebound hyperglycemia and weight gain
Once the hypoglycemia has been reversed, the person should have the usual meal or snack that is due at that time of the day to prevent repeated hypoglycemia. If a meal is >1 hour away, a snack (including 15 g carbohydrate and a protein source) should be consumed
ECG screening in DM?
q 3-5 years in age >40 or diabetes complications
Kidney screening frequency in DM?
eGFR and ACR yearly, more frequent if abnormal
How often to screen for retinopathy in person with T2DM?
Every 1-2 years
If a person is on a sulfonylurea and you’re starting insulin, what do you do with the sulfonylurea dose?
↓dose 50% or
dose AM if basal insulin; stop if
prandial insulin
Can you start sulfonylureas if severe renal or hepatic impairment?
No, these are contraindications. With decreased renal function (eGFR <60ml/min), have increased risk of hypoglycemia d/t accumulation
