1. ENDOCRINOLOGY
Archer Online USMLE Reviews
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Archer Slides are intended for use with Archer USMLE step 3 video
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which will be addressed in a detailed way with focus on High-yield
concepts in the Video lectures.
4. TSH
Obtain screening TSH in patients with conditions
that may be explained by or worsened by
hyperthyroidism :
Unexplained weight loss
Anxiety or sleep disturbance
Tachycardia, including supraventricular
tachycardia and new onset atrial fibrillation
Osteoporosis ( always suspect and rule out
hyperthyroidism especially when osteoporosis is
worsening despite adequate therapy in the elderly)
5. TSH
Obtain screening TSH in patients with conditions that
may be explained by or worsened by hypothyroidism :
History of thyroid disease
Autoimmune disease (R/O co-existent hashimatos)
Unexplained depression
Cognitive dysfunction ( dementia, delirium)
Hypercholesterolemia ( can be secondary to
hyopthyroidism or can be worsended by it)
Unexplained constipation
Screen in early pregnancy
6. TSH
Preferred Screening test for suspected HYPO/HYPER Thyroidism
Preferred Follow-up test for patients receiving therapy for either hypo or
hyperthyrodism or pts who had thyroid cancer therapy
If TSH High possible Primary hypothyroidism or rarely, secondary
hyperthyroidism
If TSH low possible Primary hyperthyroidism or rarely, secondary
hypothyroidism
If TSH low in pt on treatment for hypothyroidism reduce dose of
levothyroxine. ( usually in increments of 25mcg each time)
If TSH high in a pt on treatment for hypothyroidism Increase dose of
levothyroxine. ( usually in increments of 25mcg each time)
If TSH low in pt on treatment for hyperthyroidism Increase dose of
Propylthiouracil/ Methimazole ( or may indicate inadequate therapy)
If TSH high in a pt on treatment for hyperthyroidism Reduce dose of
Propylthiouracil/ Methimazole ( Indicates excess antithyroid therapy.
If Radioiodine therapy was chosen, then aim is to make the pt Hypothyroid in
order to achieve good cure rates in Graves thyrotoxicosis in that case, you
need to start levothyroxine post radioiodine therapy or post surgically)
7. TFTs – Further Approach
Obtain Total and Free T4
levels, ONCE TSH comes
abnormal
8. TFTs – Further Approach
If TSH high but Free T4 low primary hypothyroidism
Usually Hashimatos thyroiditis.
In countries where Iodine deficiency is a problem, this could be due to
endemic goiter. (urine iodine low)
Iatrogenic Hypothyroidism due to Thyroidectomy or Radioiodine therapy
Drug induced Amiodarone, Lithium, Iodine {excess iodine
immediately inhibits both new hormone synthesis (by blocking
organification, known as the Wolf-Chaikoff effect) and the release of
thyroid hormone. It also decreases gland size and vascularity. This effect
is transient, however, lasting approximately 1-3 weeks}, Interferon,
Thionamides
Late phase of Post-partum thyroiditis, Subacute thyroiditis, silent
thyroiditis
9. TFTs – Further Approach
If TSH High but Free T4 also high
secondary Hyperthyroidism ( pituitary
adenomas) - rare
Get a Pituitary MRI
10. TFTs – Further Approach
If TSH high but Free T4 normal Subclinical
Hypothyroidism
Subclinical Hypothyroidism :
Treatment recommended only :
If clinical symptoms are present
If hyperlipidemia (high LDL)
If patient has goiter or
If TSH > 10mU/l , For TSH between 5 to 10 obtain
TPO antibodies and consider treatment if TPO antibodies
high) In cases of subclinical hypothyroidism, presence
of anti-TPO antibodies predicts progression to overt
Hypothyroidism ( Hashimato’s)
11. TFTs – Further Approach
If TSH low but Free T4 high primary hyperthyroidism
Usually Graves Thyrotoxicosis ( Thyroid scan – homogenous,
diffuse uptake)
Toxic Multinodular Goiter ( Thyroid scan – Heterogenous)
Toxic Solitary Adenoma
Early phase of Subacute Thyroiditis/ Silent Thyroiditis ( No
Uptake on Thyroid scan)
Post-partum Thyroiditis ( painless, may be followed by
hypothyroid phase)
Iatrogenic Hyperthyroidism due to excess levothyroxine therapy in
a hypothyroid patient
Surreptious intake of Thyroid hormones
Struma Ovarii ( Increased pelvic uptake on whole body iodine
scan)
Gestational Thyrotoxicosis ( Increased HCG is responsible,
Nuclear imaging contraindicated here)
Amiodarone induced ( two types of thyrotoxicosis)
12. TFTs – Further Approach
If TSH low but Free T4 also low secondary
Hypothyroidism ( pituitary adenomas
causing compression, craniopharyngioma)
clues are headaches, visual field deficits,
ophthalmoplegia), pituitary/ hypothalamic
surgery, pituitary/ hypothalamic infection/
infarction Next step, get a Pituitary MRI
13. TFTs – Futher Approach
If TSH low but Free T4 normal get T3 level.
If T3 high T3 toxicosis.
If T3 normal Subclinical Hyperthyroidism Get
an RAIU scan to see if this is Graves or a Toxic
adenoma .
Subclinical hyperthyroidism can be just followed if no
clinical symptoms and if there is no significant reason to
treat.
Treatment of subclinical hyperthyroidism is recommended
in cases of osteoporosis ( Thyroxine increases bone resorption)
In atrial fibrillation
in elderly due to risk of atrial fibrillation and osteoporosis.
(If Graves, thionamide or I131. If Toxic adenoma, I131 is
preferred.)
14. TFTs
Remember any combinations of TSH/Free T4
can occur in severe nonthyroidal illness
depending on the phase of the illness ( critical
phase, recovery phase) Euthyroid sick
syndrome . Some combinations
low TSH, Normal free T4 ( may look
like subclinical hyperthyroidism)
High TSH, Normal free T4 ( recovery
phase, may look like subclinical hypothyroidism)
Your clue to answer questions in such situations
is the history recent or ongoing critical illness.
17. Classification of Thyrotoxicosis based on
RAIU Scan
High RAIU Low RAIU
Graves' disease Subacute thyroiditis
Toxic multinodular
goiter*
Painless thyroiditis (includes postpartum
thyroiditis)
Toxic adenoma* Chronic thyroiditis with transient thyrotoxicosis
HCG-mediated
(choriocarcinoma)
Iatrogenic/surreptitious thyroid hormone
TSH-secreting pituitary
tumor
Metastatic functional follicular thyroid cancer
(after thyroidectomy)
Amiodarone-induced thyroiditis
Struma ovarii (uptake in pelvis)
18. Grave’s Disease
Features : Diffuse Goiter, Ophthalmopathy ( proptosis, extraocular muscle paralysis, peri-
orbital edema are specific. Lid-lag and stare can occur with any hyperthyroidism ) and
Dermopathy (pre-tibial myxedema) .
Diagnosis : clinical features of hyperthyroidism ( palpitations, sweating, diarrhea, anxiety,
tremor, hairloss, weightloss, menorrhagia) + diffuse goiter, thyroid bruit/thrill can be heard
due to hyperdynamic circulation and increased thyroid vascularity.
Pain usually absent in thyroid ( PAIN may be present in subacute thyroiditis)
Always r/o subacute thyroiditis in differential
Obtain RAIU scan Graves shows homogeneous uptake where as no
uptake in subacute thyroiditis/ Surreptious intake of LT4. { Measure serum
thyroglobulin and ESR to distinguish subacute thyroiditis (elevated thyroglobulin
and ESR) from surreptitious thyroid hormone ingestion (suppressed thyroglobulin,
normal ESR)}. Painless thyroiditis has elevated thyroglobulin but normal ESR.
TSH low, Free T4 high.
Antibodies present Thyroid stimulating antibodies ( TSIgs) are high and are
responsible for goiter and hyperthyroidism. Anti-TSH antibodies, Anti-TPO
antibodies.
Can be associated with other autoimmune diseases Vitilgo, pernicious anemia
19. Treatment Options
Treatment options in Hyperthyroidism :
Medications ( Antithyroid drugs - PTU, Thionamides i.e;
methimizole ) , B-Blockers ( propranolol, atenolol) for
symptoms. ( propranolol preferred because it can block T4 to T3
conversion in high doses)
Raioactive iodine therapy (131 I)
Surgery ( Thyroidectomy)
Consider the following when selecting treatment for
thyrotoxicosis:
Patient preference
Patient's age and comorbidities
Severity of thyrotoxicosis
Goiter size
Presence of ophthalmopathy (in Graves' disease patients)
20. Treatment for Thyrotoxicosis Due to Overproduction of Thyroid Hormone
Modality Advantages Disadvantages
Antithyroid drug
therapy
Least invasive
Least costly
Lower risk of permanent hypothyroidism
Potential beneficial immunomodulatory
effects
Adverse drug effects
Low permanent remission rate
(approximately 33%-50%)
Radioiodine Moderately fast reduction in thyroid
hormone levels
Less invasive than surgery
Permanent hypothyroidism likely
Requires delay in pregnancy (6-12 months)
and breastfeeding
May precipitate new or worsened
ophthalmopathy
Slight risk of thyroid storm after treatment (
in severe Hyperthyroidism, use pre-
treatment)
Thyroidectomy Rapid reduction in thyroid hormone levels
Allows concurrent removal of suspicious
nodules (if present)
Allows reduction in size of large goiters
Most invasive
Most costly
Permanent scar
Permanent hypothyroidism likely
Potential injury to parathyroids and recurrent
laryngeal nerve
21. Anti-thyroid drug therapy
Propyl thiouracil :
Typical starting dose 100mg tid
Will need to discontinue 2 weeks prior to Radioiodine therapy because
it can lead to failure of the therapy as it inhibits roadioiodine uptake by
thyroid. ( REMEMBER METHIMIZOLE WILL NOT MUCH
AFFECT RADIOIODINE UPTAKE – So, it is the preferred therapy
to start if I131 therapy is planned but stop it 3 days prior to I131)
LESS POTENT than Methimizole.
Preferred drug in severe Hyperthyroidism because it can block T4 to T3
Conversion ( this effect not seen with methimazole)
Side effects : Rash, Agranulocytosis, Hepatocellular necrosis
Safe in pregnancy ( as it highly binds to plasma protein and very little
crosses placenta. There is NO risk of Aplasia Cutis). However, Fetal
hypothyroidism can occur in high doses due to transplacetal passage.
MONITOR LFTS AND CBC If pts have sorethroat/ infection etc
suggesting possibility of agaranulocytosis d/c PTU and get a blood
count
22. Anti-thyroid drug therapy
Methimizole :
More potent than PTU
Typical starting dose is 30mg/d – preferred drug for most patients
because single daily dose (except for patients with allergy to
methimazole, who are pregnant, or have severe thyrotoxicosis or thyroid
storm)
Contraindicated in pregnancy due to risk of Aplasia cutis and higher
transplacental spread than PTU.
Not preferred in breast feeding ( PTU is preferred in breast feeding)
Side effects : Rash, Agranulocytosis, cholestatic jaundice
Good for pre-treatment prior to I-131 therapy. ( pre-treatment is used to
normalize thyroid function before the administration of radioiodine and
to attenuate potential exacerbations following ablative radioiodine
therapy. recommended for the elderly and those with underlying
cardiac disease, who may be more vulnerable to worsening
thyrotoxicosis during I 131 therapy.). Stop pre-treatment with
methimazole 3 days prior to I131 to prevent treatment failure. Restart 3
days after giving I131 ( I131 takes 12 to 15 weeks to correct
hyperthyroidism – monitor free T4 after I131 Therapy)
PTU is preferred over methimizole in severe hyperthyroidism.
IF USING ANTITHYROID THERAPY as sole primary
therapy use for at least 12-18 months before tapering.
When started, Thionamides can correct hyperthyroidism in
about 4 to 8 weeks ( response expected in 4 to 8 wks)
23. Antithyroid drug therapy
For Grave’s disease patient getting only anti
thyroid drug therapy, factors favoring remission
are :
- Small goiter
- Low T3/T4 ratio
- Mild thyrotoxicosis
- Negative TSH-receptor antibody titers after
treatment
- No prior relapse
So, antithyroid drug therapy can be a
preferred modaility in these scenarios.
24. Aplasia Cutis
Absence of skin in the newborn
Can occur with Methimizole use during
pregnancy.
PIC : Aplasia Cutis of scalp
25. Radioiodine therapy
Select a dose of radioiodine based on the size of the patient's
goiter and the result of the RAIU test.
Do not use radioactive iodine in patients who are pregnant
(absolute contraindication) or breastfeeding.
Pregnancy should be delayed four to six months after
radioiodine therapy.
Radioiodine is better avoided in patients with Graves'
ophthalmopathy.
( may cause worsening of ophthalmopathy)
After Radioiodine therapy
mother should stay away from children at least for 7 days (
Mother need to Arrange for a care taker for baby).
A I131 recepient must avoid contact with pregnant women,
avoid sexual contact for one week after the therapy
26. Radioiodine Therapy – Follow Up
Hypothyroidism is inevitable in most cases. The risk of Hypothyroidism depends
on the dose of I131.
About 2/3 of the patients develop hypothyroidism in the first year after I131.
Even if they do not develop hypothyroidism in the first year, the TSH should be
followed every 6 months forever after I131 therapy since the risk of developing
hypothyroidism persists for lifetime
Get free T4 in the early period after I131 therapy not TSH. TSH can be
misleading in that it can remain low for about 4 to 6 weeks even when patient’s
free T4 returns to normal and patient is clinically euthyroid.
I131 typically takes 12 to 15 weeks to correct hyperthyroidism. So, thionamide has
to be restarted 3 days after I131 and Free T4 and TSH carefully monitored. Once
there is evidence of euthyroid state, taper and stop thionamide. Follow TSH, if
hypothyroidism sets in start Levothyroxine)
Start Levothyroxine after getting TSH level and Free T4 if the levels are consistent
with hypothyroidism .
27. Surgery
Especially preferred in :
Goiter causing obstructive symptoms
Pregnant women allergic to PTU or develop agranulocytosis on PTU ( Radio
iodine is not an option in pregnancy)
Intolerance to thionamides; refusal to take antithyroid drugs or radioactive iodine
Recurrence after a trial of thionamide therapy for Graves’ disease
Large MULTI-NODULAR goiter
Suspicion of malignancy.
Patients should be made euthyroid with thionamide therapy prior to
elective surgery. Once a euthyroid state is achieved, oral iodine is given
7 to 10 days preoperatively to reduce the vascularity of the gland
then total/ subtotal thyroidectomy.
Complications : Hypothyroidism inevitable, Recurrent laryngeal nerve
palsy (1%) , Permanent hypoparathyroidism ( 1% risk) and 1% risk of
recurrent hyperthyroidism
Admit pts to ICU for 24 hrs s/p surgery Monitor calcium level
q6hrs in patents s/p thyroid surgery and replete calcium aggressively if
<7mg%
28. Follow-up
In pts on long term antithyroid drug therapy
Monitor for adverse effects of antithyroid drugs such as rash,
hepatic dysfunction, and agranulocytosis.
Repeat thyroid function tests every 3 to 6 months for the first
year and then every 6 to 12 months after attaining normal
FT4 and TSH levels.
Follow serum FT4 and TSH levels at 4-week intervals
to ensure adequate replacement therapy ( for
hypothyroidism) immediately after radioiodine therapy.
29. Q1
A 58-year-old woman has anxiety, tremors, excessive sweating, palpitations, and
insomnia of approximately 1 month’s duration. Her medical history is unremarkable.
She has had no recent pregnancies or miscarriages. She has a modest, nontender goiter
and no exophthalmos. She takes no medications and has had no recent radiologic
procedures. The
24-hour radioactive iodine uptake is 10% (normal, 20% to 35%).
Laboratory Studies
Erythrocyte sedimentation rate 8 mm/h
Free thyroxine 3.5 ng/dL
Thyroid-stimulating hormone < 0.01 μU/mL
Thyroglobulin 45 ng/mL (normal, 2 to 20 ng/mL) ( do not confuse thyroglobulin with
thyroid binding globulin – thyroglobulin is the one present in the thyroid follicles and
is released out and elevated whenever there is “thyroidITIS”
Antithyroperoxidase 26 (normal, <2 μU/mL)
What is the most likely diagnosis?
( A ) Struma ovarii
( B ) Recent imaging study with an iodinated contrast
( C ) Subacute thyroiditis
( D ) Surreptitious use of thyroid hormones
( E ) Painless/silent thyroiditis
(F) Use of Amiodarone
30. Q2
A 58-year-old woman presents to your office with increasing fatigue, memory loss,
and depression for the past one year. Her history is significant for hypertension and
she takes enalapril for it. Her family history reveals a brother who takes a medication
for his thyroid. On physical examination, she is 168 cm (66 in) tall and weighs 73 kg
(162 lb). Blood pressure is 152/88 mm Hg and heart rate is 86/min. HEENT exam is
nornal without any thyroid enlargement.
Laboratory Studies
Hematocrit 46%
Plasma glucose 82 mg/dL
Total cholesterol 255 mg/dL
High-density lipoprotein cholesterol 49 mg/dL
Low-density lipoprotein cholesterol 187 mg/dL
Thyroid-stimulating hormone 12.2 μU/mL
A free thyroxine level of 0.9 ng/dL.
Which of the following statements is correct about levothyroxine replacement
therapy for this patient?
( A ) Her LDL will decrease.
( B ) There will be no improvement in her symptoms.
( C ) She is likely to lose weight.
( D ) She will be at an increased risk of atrial fibrillation
( E ) she will have an increased risk of osteoporosis
31. ANS.A
This patient has subclinical hypothyroidism. Rx
is recommended if serum TSH levels greater
than 10 μU/mL. Also, Rx is recommended in
patients having symptoms and effects of
hypothyroidism like hyperlipidemia In such
cases, levothyroxine therapy reduces LDL
cholesterol levels and improves symptoms.
32. Q3
A 50 y/o HIV +ve man with a CD4 count of 200 prrsents with complaints of
fatigue, weightloss and dry cough. Cough has been for past 2 days and has
high grade fever. No chest pain but he is visibly short of breath. His ABGs
revealed hypoxemic respiratory failure with a po2 of 45. He is started on
Bactrim IV and steroids.
Laboratory Studies reveal
Free thyroxine 0.9 ng/dL
Triiodothyronine 22 ng/dL
Thyroid-stimulating hormone 0.3 μU/mL
Which of the following statements about this patient’s condition is true?
( A ) Perform a radioactive iodine uptake test
( B ) Using T3 treatment will improve his condition and prognosis.
( C ) The lab abnormalities are due to decreased peripheral conversion of thyroxine to
triiodothyronine
( D ) Serum thyroid binding globulin is increased
( E ) Pituitary MRI should be obtained
34. Euthyroid Sick Syndrome
Euthyroid sick syndrome is seen in acutely and
critically ill patients.
Occurs due to alterations in the levels of
circulating thyroid hormones that can occur in
severe nonthyroidal illnesses.
Features: low T3, high reverse t3 normal T4,
and low TSH levels. TSH starts elevating to
hypothyroid levels during “recovery” phase of
non thyroidal illness and returns to normal with
complete recovery. But many combinations can
occur
35. Q4
A 32-year-old woman is evaluated for recent onset of fatigue, palpitations,
profuse sweating, and emotional lability. She gave birth to her second child 8
weeks ago and is not breast feeding. On physical examination, her pulse rate
is 100/min, and she has mild lid lag, a fine hand tremor, and a slightly
enlarged, nontender thyroid gland. Radioactive iodine uptake is less than 1%
at 4 and 24 hours (normal, 20% to 35%). Laboratory test results include a
serum thyroid-stimulating hormone level of less than 0.03 μU/mL and a free
thyroxine level of 3.8 ng/dL.
Which of the following is the optimal treatment for this patient?
( A ) Antithyroid drugs
( B ) Radioactive iodine
( C ) Thyroidectomy
( D ) Prednisone
( E ) ß-blockers
36. Key Point
Women presenting with thyrotoxicosis are treated with beta
blockers to decrease palpitations tremors..
Antithyroid medications are not used in the thyrotoxic phase as
since thyroid is not overactive.
Post partum thyroiditis may be followed by a hypothyroid phase
( due to destruction – which may start 4-8 months post-partum
and may last 9-12 months) - treated with thyroid hormone
replacement which should be later tapered off It is always
important to monitor and taper off thyroid hormone after
postpartum thyroiditis, since 80% of patients will regain normal
thyroid function and not require chronic therapy.
37. IMP! – AIT
This condition occurs in up to 10% of patients who use
amiodarone, which has a very high iodine content. Two subtypes
occur: type 1 AIT is caused by iodine overload and occurs
primarily in patients with underlying goiters; type 2 AIT is caused
by drug-induced thyroid follicular damage (thyroiditis).
Both types are associated with a low 24-hour radioactive iodine
uptake. No tests reliably distinguish between the two subtypes,
although an underlying goiter and detectable radioactive iodine
uptake are more common in type 1
AIT. Treatment of type 1 AIT consists of administering
thionamides, with or without potassium perchlorate
Type 2 AIT may respond to corticosteroid therapy.
Patients who do not respond to this treatment may require
plasmapheresis, dialysis, or thyroidectomy.
38. A 70-year-old man is evaluated because of a 1-year history of progressive weakness,
weight loss, and hand tremors. For nearly 3 years, he has been treated with amiodarone
for paroxysmal atrial flutter. He has no goiter and no history of thyroid disease.
Thyroid scan shows scant, patchy tracer uptake. The 24-hour radioactive iodine uptake
is 2.7% at 6 hours and 4.1% at 24 hours (normal, 20% to 35%). The serum thyroid-
stimulating hormone level is <0.01 μU/mL and the serum free thyroxine level is 3.8
ng/dL.
Which of the following statements is true about the effects of amiodarone on
this patient’s thyroid function?
( A ) Amiodarone can cause thyrotoxicosis by producing iodine overload or thyroiditis.
( B ) Amiodarone blocks peripheral thyroid hormone receptors.
( C ) Amiodarone increases peripheral conversion of thyroxine to triiodothyronine.
( D ) Amiodarone directly suppresses pituitary secretion of thyroid-stimulating
hormone.
( E ) Amiodarone increases serum thyroid hormone protein binding.
39. Two subtypes of amiodarone-induced
thyrotoxicosis occur: type 1 is caused by iodine
overload and occurs primarily in patients with
underlying goiters; type 2 is caused by drug-
induced thyroid follicular damage (thyroiditis).
41. Hashimato’S Thyroiditis
Autoimmune thyroiditis associated with lymphocytic
infiltration of thyroid gland. causes gland disruption,
initially may lead to hashitoxicosis and then
hypothyroidism
Diagnosis : HIGH TSH, LOW FREE T4 and Elevated
TPO antibodies/ anti microsomal antibodies.
TSIgs may be present too
Diffuse Goiter on physical exam.
Association with other autoimmune diseases must be
kept in mind pernicious anemia, addisons disease
Can be associated with B cell lymphomas
42. Treating Hypothyroidism
Levothyroxine (LT4) drug of choice.
In young patients start initial full replacement dose
calculated as 1.6 µg/kg/d. ( 70kg man – 112mcg/d)
In obese patients calculate the initial dose using ideal
body weight of course , you can follow-up serum TSH
6-8 weeks later and titrate the dose.
In elderly patients > 60 yrs of age start at dose 25 to 50
mcg and titrate every 6-8 wks untill TSH comes to desired
range.
In those with KNOWN CAD/ hx of CHF and
arrhythmias Start at 12.5 mcg to 25 mcg dose and then
titrate every 6-8 wks untill TSH comes to desired range.
44. Follow up – Treatment adequacy
TSH is used to follow up treatment adequacy
Levothyroxine has a t 1/2 of 7days. It takes a
drug four to five t1/2s to reach steady state
which means DO NOT INCREASE LT4 dose
prior to 4 to 6 weeks if pt is not symptomatic.
TSH level should be obtained at 6 – 8 weeks
after starting therapy because it takes this
time for raised to TSH to normalize and also
this is the time at which you can properly assess
adequacy of LT4 therapy because LT4 reaches
steady state around this time.
45. Follow up – Treatment adequacy
Use TSH levels as the guide to thyroid hormone dosage
requirements.
Once treatment is started, monitor serum TSH levels
every 6 to 8 weeks and adjust the LT4 dose until the
TSH value is in the desired range.
Once TSH reaches desired range, recheck the
TSH level 3 to 6 months later, and then if normal
recheck annually.
If the TSH value is above the normal range, increase
the LT4 dose by 12.5 to 25 µg/d and recheck in 6 to 8
weeks.
If the TSH value is low, decrease the LT4 dose by
12.5 to 25 µg/d and recheck in 6 to 8 weeks
46. Recognize Interactions!
Counsel patients to take levothyroxine at the
same time each day and to avoid taking it within
4 hours of iron tablets, calcium supplements,
antacids, and fiber supplements ( can reduce
LT4 absorption)
47. Lithium Induced
Li Can cause hypothroidism
Rx do not discontinue lithium, Start
levothyroxine and continue lithium therapy.
48. Myxedema Coma
Severe hypothyroidism associated with altered mental
status/ delirium/ coma.
Myxedema coma usually found in elderly patients who
have untreated or inadequately treated hypothyroidism
and then develop a precipitating event. ( precipitating
event for myxedema coma in a pt with
untreated/inadequately treated hypothyroidism can be
SEPSIS, Surgery, Trauma, GI bleeding, Stroke, MI, CHF,
Sedative use)
So, always evaluate the pt for precipitating factor also
treat both myxedema coma as well as precipitant.
49. Myxedema coma
Admit to ICU for careful monitoring and appropriate
treatment.
Get Endocrine consult always.
Obtain blood cultures, CT head, cardiac enzymes, EKG,
CHEM 18, CBC R/o preciptating factors
TSH, FREE T4
RX :
Vital support : intubation if prolonged coma for airway protection, IV
fluids, hypothermia blanket.
Levothyroxine intravenosly (500 µg, then 50-100 µg/d for myxedema
coma, for npo pts 80% of oral dose ) + hydrocortosine 100 q8hrs x
2days to address possible decreased adrenal reserve in myxedema.
Also can use combination of LT4+LT3 for rapid T4 and T3 repletion
in myxedema coma
Look for and treat any precipitating factor
51. Approach – Palpable Thyroid Nodule
If thyroid nodule palpable
Get TSH First.
If High TSH – suggests cold nodule/ Hashimatos Get FNAC ( some
recommend ultrasound as next step here because hashimatos may have
benign nodularity that regress with therapy and ultrasound will help to see
if there are suspicious features. If U/S suspicious, then FNAC is
recommended. This may be optimal approach because hurthle cells of
hashimatos may cause false positives on cytology if the FNAC is obtained
from such benign nodule). Treat with levothyroxine if overt hypothyroidism
or subclinical hypothyroidism that warrants treatment.
If TSH normal – suggests cold nodule - get FNAC next
If TSH low - suggests Hot nodule ( toxic adenoma) but not confirmative
(What if there is GRAVES in the surrounding tissue and this is a cold
nodule?) so, next step get RAIU scan if COLD nodule, get FNAC. If
RAIU scan shows Hot nodule treat with I131 ( if there is overt
hyperthyroidism from this toxic adenoma) or just observation.
Cold nodules are more likely to be malignant when compared to hot nodules ( hot/
functioning nodule virtually rules out malignancy)
A negative FNAC does not rule out cancer completely. So, if clinical suspicion for
cancer is high consider surgical excision of the entire nodule. ( especially, when
histology revealed follicular adenoma – remember, a negative FNAC from one area
may not rule out possibility of follicular carcinoma in follicular adenoma )
52. Approach – Thyroid Incidentalomas
Thyroid Incidentalomas – These are those nodules ( not the palpable
ones) detected on ultrasound such as ultrasound done for other
palpable thyroid abnormalities, during carotid artery imaging or
ultrasound done for hyperparathyroidism).
FNAC indicated if
Nodule > 10 mm in diameter.
On ultrasound, if nodule has suspicious features of malignancy
hypoechoic, microcalcifications, irregular shape, blurred margin or
increased vascularity
If there are risk factors for thyroid cancer ( family history, childhood
neck irradiation)
53. After FNAC - Further Approach
If FNAC is benign
Cystic nodule – use percutaneous Ethanol injection to get rid of nodule
Solid Nodule – use suppressive therapy with levothyroxine if there are no
contraindications ( Heart disease, old age). Suppressive therapy with LT4
aims to reduce TSH and there by, regress the nodule
If FNAC is malignant SURGERY
If FNAC is follicular adenoma (benign) get a thyroid
scan if not already done If this is hot/functioning
nodule, it rules out malignancy – so, follow-up. If this is a
cold nodule, a negative FNAC from one area may not rule
out possibility of follicular carcinoma in follicular adenoma
– so, do Surgical excision of the entire nodule
(sub-total thyroidectomy) in those cases.
If FNAC is non-diagnostic repeat FNAC
55. Thyroid Cancer - Prevalence
Prevalence of thyroid cancer is higher in the
following groups and hence, high clinical suspicion
should be maintained if you find a thyroid nodule
in these groups ( i.e; warrants further evaluation of
the nodule):
Children
Adults less than 30 yrs or above 60 yrs of age
History of head and neck radiation (eg: Hodgkins )
Family history of thyroid cancer
56. Radiation Exposure – Follow up for
detecting thyroid cancer
Guidelines are not clear.
The incidence of thyroid cancer after radiation exposure is high for
about four decades after exposure and then it declines.
If there is a history of significant radiation exposure such as (
therapeutic external beam radiation therapy in children, survivors of
Japan atomic bombing, exposure during chernobyl nuclear incident),
physical examination by thyroid palpation and ultrasound should be
obtained every three years to detect any nodules.
If there is a palpable nodule in these patients, ultrasound must still
be obtained to detect any non palpable nodules ( because multiple
nodules are a common finding in radiation exposed patients)
All palpable nodules and suspicious nodules on ultrasound, must
undergo FNAC.
58. Pheochromocytoma
Consider evaluating for Pheochromocytoma in patients with:
Refractory hypertension
Hypertension, accompanied by hyperadrenergic spells with:
Nonexertional palpitations
Diaphoresis
Headache
Tremor
Pallor
Family history of familial pheochromocytoma
A genetic syndrome that increases the risk of pheochromocytoma, such as:
Multiple endocrine neoplasia type 2
von Hippel-Lindau disease - RCC
Neurofibromatosis type 1
History of gastric stromal tumor or pulmonary chondromas (Carney triad)
An incidentally discovered adrenal mass ( Adrenal Incidentalomas)
59. Pheochromocytoma
Episodic Hypertension is charecterestic but
ORTHOSTATIC HYPOTENSION can be
seen.
Pheochromocytomas are 10% tumors 10%
malignant, 10% bilateral and 10% familial.
60. Pheochromocytoma - Diagnosis
Best diagnostic test and high specificity (99%) 24 hr Urinary
Metanephrines ( metanephrines or normetanephrines above the
upper limit of normal in a patient not taking an interfering
medication and not physically stressed is consistent with
pheochromocytoma )
Plasma Metanephrines can be used if 24 hr unrine collection is not
possible –specificity (88%) lower than 24 hr urine metanephrines
Obtain CT Abdomen to r/o Adrenal mass only if biochemical tests
are positive. Very sensitive (96%) for pheochromocytoma ( adrenal
mass) but low specificity due to high prevalence of adrenal
incidentalomas.
MIBG scan Very specific for pheochromocytoma. Sensitivity
lower than CT scan. (Sensitivity only 80% and specificity 100%)
MIBG (Metaiodobenzylguanidine) scan is the best test if looking for
extra adrenal pheochromocytomas
Other tests – Plasma catecholamines, Urine VMA
61. False + ves
Medications and activities that may increase measured levels of
catecholamines and metabolites ( False +ves for Metanephrines/
VMA)
Tricyclic antidepressants
Labetalol
Levodopa
Drugs containing catecholamines (e.g., decongestants)
Amphetamines
Buspirone (and most psychoactive agents)
Sotalol
Withdrawal from clonidine hydrochloride and other drugs
Ethanol
Acetaminophen and phenoxybenzamine (fractionated plasma
metanephrines)
Physical stress (e.g., stroke, obstructive sleep apnea)
62. Treatment
Acute Hypertensive crises use IV Phentolamine,
Sodium nitroprusside or Nicardipine.
Definitive treatment is SURGERY. Send for histopath
to r/o malignancy.
REMEMBER TO USE BOTH ALPHA AND BETA
ADRENERGIC BLOCKING AGENTS PRIOR TO
SURGERY – to prevent hypertensive crises during
surgery. ( use phenoxybenzamine + atenolol)
Do not use non selective beta blocker without alpha
blocker ( eg: propranolol alone)
Understand that relatively short-acting, selective α1-
adrenergic receptor blockers (e.g., prazosin, terazosin,
doxazosin) may be inadequate for preoperative drug
preparation so phenoxybenzamine preferred for pre-
op therapy as it is long acting.
64. Hypercalcemia
Etiology
Clinical features : bones, moans, stones, groans
Investigations: Ca, Phos, EKG, PTH, 24 hr Urinary calcium excretion or spot
urine calcium/creatinine ratio ( R/o familial hypocalciuric hypercalcemia)
Management:
Criteria for surgery in primary hyperparathyroidism
Sestamibi scan only if surgery is planned/indicated
Hypercalcemic crisis management – ivf + lasix after volume repletion only
Indications for corticosteroids : are useful for treating hypercalcemia caused
by vitamin D toxicity, certain malignancies (eg, multiple myeloma, lymphoma),
sarcoidosis, and other granulomatous diseases
Cinacalcet (Sensipar) -- Directly lowers parathyroid hormone (PTH) levels by
increasing sensitivity of calcium sensing receptor on chief cell of parathyroid
gland to extracellular calcium. Also results in concomitant serum calcium
decrease Indicated for hypercalcemia with parathyroid carcinoma.
Do not lower Calcium too much Serum calcium reduction may cause lowered
seizure threshold, paresthesia, myalgia, cramping, and tetany;
65. Criteria for Surgery – Primary
hyperparathyroidism
Serum total calcium level >12 mg per dL (3 mmol per L) at any time
Hyperparathyroid crisis (discrete episode of life-threatening
hypercalcemia)
Marked hypercalciuria (urinary calcium excretion more than 400 mg
per day)
Nephrolithiasis
Impaired renal function
Osteitis fibrosa cystica
Reduced cortical bone density (measure with dual x-ray
absorptiometry or similar technique)
Bone mass more than two standard deviations below age-matched controls (Z
score less than 2)
Classic neuromuscular symptoms
Proximal muscle weakness and atrophy, hyperreflexia, and gait
disturbance
Age younger than 50
66. A 66-year-old asymptomatic woman is evaluated for a serum
calcium level of 11 mg/dL detected during a routine screening
examination. Subsequently, the ionized calcium level is 5.7
mg/dL, and the intact parathyroid hormone level is elevated.
Which of the following is the most appropriate next step in
the management of this patient?
( A ) Parathyroidectomy
( B ) Sestamibi scan of the parathyroid glands
( C ) Creatinine clearance and 24-hour urine calcium excretion
( D ) Chest radiograph
( E ) Estrogen replacement therapy
68. Remember!
“If suspecting Prolactin secreting adenomas or
while working up the cause of
hyperprolactinemia, the LEVEL OF
PROLACTIN is the best clue to the possible
etiology of hyperprolatinemia”
Prolactin level usually less than 100 with drugs
or stress!
69. Prolactinomas
Microademomas prolactin levels usually > 100
Macroadenomas Prolactin levels usually very high
500 to 1000. Be aware of HOOK Effect.
MRI is the next test if high prolactin level encountered
and cannot be explained by meds/ stress. MRIs do not
r/o small microadenomas (<3mm)
For microadenomas/ non invasive macroadenomas
use Bromocriptine ( dopamine agonist) Consider
surgery for those patients not responding to or
intolerant of dopamine agonists.
If Prolactin Producing Macroadenomas with mass
effect Try bromocriptine first if no response,
Surgery ( trans sphenoidal resection)
70. Pituitary Adenomas
In deciding how to approach INCIDENTALLY
discovered pituitary tumors, first rule out Function
R/O functioning adenomas first prolactin level,
Dexamethasone suppression test, ACTH level, TSH
and IGF 1 level depending on the clinical features.
Except Prolactinomas, all other functioning adenomas
are treated primarily by surgery
If Non functioning adenomas Surgery indicated only
if mass effects Visual field defects , Headaches and
Hypopituitarism
Follow patients with non functioning microadenomas
and small, noninvasive macroadenomas with a 6-month
MRI scan and yearly thereafter If there is no
evidence of enlargement after 3 to 5 years, then
continue to follow patients clinically.
71. A 25-year-old woman is evaluated because of a 9-month history of weight gain,
fatigue, muscle weakness, and depression. She bruises and bleeds easily, and her
menses have been irregular. Her medical history and family history are unremarkable.
On physical examination, she is 157 cm (62 in) tall and weighs 74 kg (164 lb). Blood
pressure is 160/95 mm Hg and pulse rate is 84/min. She has a rounded, plethoric face.
Her supraclavicular fat pads are notably full, and she has a mildly enlarged dorsal fat
pad (buffalo hump). She has several violaceous striae on the lower abdomen
and bruises on the left arm from recent blood testing.
Laboratory Studies
Urine cortisol 318 μg/24 h
Morning serum cortisol 28 μg/dL
Morning plasma adrenocorticotropic hormone 45 pg/mL
After administration of dexamethasone, 8 mg orally at bedtime, the morning serum
cortisol level is 3 μg/dL. Findings on chest radiograph are normal.
Which of the following tests should be ordered next?
( A ) Low-dose (1 mg) overnight dexamethasone suppression test
( B ) Magnetic resonance imaging scan of the pituitary gland
( C ) Computed tomography scan of the adrenal glands
( D ) Computed tomography scan of the lungs
( E ) Inferior petrosal sinus sampling
72. CARCINOID
-Flushing, diarrhea, wheezing are clinical features
-Ileal carcinoids commonly metastisizes to liver
-Appendiceal carcinoids are most common.
-If pt develops above symptoms on small doses of SSRIs
suspect Carcinoid syndrome
-Screening test Urine 5-HIAA
-Confirmatory test – Octreotide Scan
-Rx – medically, octreotide for symptoms
-Surgery is definitive if no metastases
75. A 38-year-old woman is evaluated while in a stuporous state. The patient is slender
and nearly comatose. She responds minimally to a loud voice and sternal pain. On
physical examination, the pulse rate is 110/min and blood pressure is 115/70 mm Hg.
An accompanying friend informs you that the patient is a nurse and that she has had
recent psychiatric problems. The blood glucose level is 14 mg/dL. Additional blood is
drawn, and the patient is quickly resuscitated with intravenous glucose. A sulfonylurea
screen is negative.Laboratory Studies
Serum calcium 9.5 mg/dL
Serum insulin 45 mU/mL
C-peptide 4.2 ng/mL (normal, 0.5 to 2.0 ng/mL)
Proinsulin 0.6 ng/mL (normal, 0 to 0.2 ng/mL)
Which of the following is the best explanation for these findings?
( A ) Solitary insulin-producing pancreatic islet cell tumor
( B ) Surreptitious insulin use
( C ) Surreptitious metformin use
( D ) Multiple endocrine neoplasia type 1
( E ) Multiple endocrine neoplasia type 2A
76. The differential diagnosis of fasting
hypoglycemia associated with hyperinsulinemia
includes insulinoma, surreptitious insulin use,
and oral sulfonylurea ingestion.
Surreptitious insulin use is associated with low
serum C-peptide and proinsulin levels.
78. Congenital Adrenal
Hyperplasia
21 Hydroxylase deficiency
Increased 17 hydroxy progesterone, increased adrenal
androgens. Low cortisol
Ambiguous Genitilia in Congenital form
Needs Mineralocorticoid and Glucocorticoid replacement –
prevent salt wasting and hypotension
Adult onset CAH is possible in mild deficiency – can be
confused with PCOS
80. Conns Syndrome
Primary Hyperaldosteronism – Hypertension, Hypokalemia
and Alkalosis
PAC/ PRA ratio best screening test
CT scan to r/o adrenal mass after biochemical evidence.
Rx – medically with Spironolactone
Surgery if tumor > 4cm or suspicious features of adrenal
cancer or if refractory HTN despite maximal medical therapy
82. False +ve Low Dose dexamathasone
test
Factors that can produce false-positive or false-negative
dexamethasone suppression tests:
Alcohol, rifampin, phenytoin, and phenobarbital induce
the cytochrome P450-related enzymes and enhance
dexamethasone clearance Cause False +ve
Hepatic failure retards dexamethasone clearance
cause false –ve.
In renal failure, serum cortisol may appear
nonsuppressible by dexamethasone
Obesity and depression give false-positive results
Thiazolidinediones can give false-negative results
85. Work-up
In all Adrenal incidentalomas, R/o functioning
adenomas first
Do Low dose dexamethasone test (1mg) and Plasma
metanephrines in all patients
Do PAC/PRA only if HTN is present or if serum
potassium is low.
If Functioning adenomas – Rx is usually surgery
( except in Conns Syndrome where medical Rx
can be tried first)
86. Work-up
For non-functioning adenomas, further
treatment depends on the size of adrenal mass.
< 4cm low risk of cancer ( 2% risk) . Follow-up
Ct scan at 6-12 months. If no change, no further
follow up.
4cm-6cm 6% risk of cancer Adrenalectomy or
a Follow-up CT Scan at 6months. If no growth, just
follow clinically. ( no more imaging)
>6cm high risk of malignancy (25% cases). Rx
with adrenalectomy
87. After a fall while horseback riding, a 37-year-old woman is evaluated with an
emergency CT scan of the abdomen. The CT scan shows no evidence of a
ruptured spleen, but shows a 2.5-cm right adrenal mass. The patient’s medical
history, including review of systems, is normal. Findings on physical
examination, including blood pressure, are unremarkable. Plasma glucose
level, serum electrolyte levels, and renal function are normal.
What is the most appropriate next step in the management of this
patient?
( A ) Surgical removal of the mass
( B ) MRI of the adrenal glands
( C ) Fine-needle aspiration biopsy of the mass under CT guidance
( D ) Repeated CT scan in 3 to 6 months
( E ) 24-Hour urinary catecholamines, metanephrine, and cortisol
88. 35-year-old man with a 10-year history of type 1
diabetes mellitus is evaluated because of recent onset of
morning hyperglycemia. For the past 10 days, his
morning blood glucose levels ranged from 220 to 300
mg/dL. He has also experienced nightmares recently.
Which of the following best explains this patient’s
morning hyperglycemia?
( A ) Diabetic nephropathy
( B ) Undertreatment with insulin
( C ) Overtreatment with insulin
( D ) Diabetic neuropathy
89. KEY POINT
SOMGYI EFFECT
Nightmares are a clue and signifies a drop in
blood glucose to low levels
Next step reduce the dose of pre-dinner
insulin