1. ENDOCRINOLOGY
Archer Online USMLE Reviews
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2. Thyroid Disorders
Thyrotoxicosis
Subacute Thyroiditis
Thyroid Function Tests
Hashimatos Thyroiditis
Hypothyroidism
Thyrotoxic periodic paralysis
Thyroid Nodule and Approach
Thyroid Cancer

3. Thyroid Diagnostic Studies
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Thyroid Function Tests : TSH, Total T4, Free T4, T3
levels.
Thyroid Binding Globulin
Thyroid Uptake Scan – Radio active iodine uptake scan
( RAIU scan)
Antibodies : Thyroid stimulating immunoglobulins,
Anti-microsomal antibodies, Anti-thyroid peroxidase
antibodies
Thyroid ultrasound
Thyroid Biopsy, FNAC

4. TSH
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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)

5. TSH
Obtain screening TSH in patients with conditions
that may be explained by or aggravated by
hyperthyroidism :
 Unexplained weight loss
 Anxiety or sleep disturbance
 Tachycardia, including supraventricular
tachycardia and new onset atrial fibrillation
 Osteoporosis

6. TSH
Obtain screening TSH in patients with conditions that
may be explained by or aggravated by hypothyroidism :
 History of thyroid disease
 Autoimmune disease (R/O co-existent hashimatos)
 Unexplained depression
 Cognitive dysfunction ( dementia, delirium)
 Hypercholesterolemia
 Unexplained constipation
Screen in early pregnancy

7. Other TFTs
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Obtain Total and Free T4 levels, ONCE TSH comes abnormal
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If TSH high but Free T4 low  primary hypothyroidism
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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
If TSH High but Free T4 also high  secondary Hyperthyroidism
( pituitary adenomas) - rare

8. 
Other TFTs
If TSH low but Free T4 high  primary hyperthyroidism
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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)

9. Other TFTs
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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

10. Other TFTs
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If TSH low but Free T4 normal  get T3 level. If
T3 high  T3 toxicosis. If T3 normal  subclinical
Hyperthyroidism.
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If TSH high but Free T4 normal  Sublinical
Hypothyroidism ( Treat only if symptoms are
present or TSH > 10mU/l , For TSH between 5 to
10  consider Rx if TPO antibodies high/ pt has
goiter or high serum LDL)
 In cases of subclinical hypothyroidism,
presence of anti-TPO antibodies predicts
progression to overt Hypothyroidism ( Hashimatos)

11. Other TFTs
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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
 High TSH, Normal free T4

12. Thyrotoxicosis
Important topics:
Graves disease
Subacute thyroiditis
Post partum thyroiditis
Amiodarone induced

14. 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)

15. Grave’s Disease
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Features : Diffuse Goiter, Ophthalmopathy ( proptosis, extraocular muscle paralysis, periorbital edema are specific. Lid-lag and stare can occur with any hyperthyroidism ) and
Dermopathy (pre-tibial myxedema) .
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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.
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Pain usually absent in thyroid ( PAIN may be present in subacute thyroiditis)
Always r/o subacute thyroiditis in differential
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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.
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TSH low, Free T4 high.
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Antibodies present  Thyroid stimulating antibodies ( TSIgs) are high and are
responsible for goiter and hyperthyroidism. Anti-TSH antibodies, Anti-TPO
antibodies.
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Can be associated with other autoimmune diseases  Vitilgo, pernicious anemia

16. Treatment Options
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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:
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Patient preference
Patient's age and comorbidities
Severity of thyrotoxicosis
Goiter size
Presence of ophthalmopathy (in Graves' disease patients)

17. 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 pretreatment)
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

18. Anti-thyroid drug therapy
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Propyl thiouracil :
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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 AFFECT
RADIOIODINE THERAPY – So, it is the preferred therapy to start if
I131 therapy is planned)
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

19. Anti-thyroid drug therapy
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Methimizole :
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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.
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.

20. Antithyroid drug therapy
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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
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So, antithyroid drug therapy can be a
preferred modaility in these scenarios.

21. Aplasia Cutis
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Absence of skin in the newborn
Can occur with Methimizole use during
pregnancy.
PIC : Aplasia Cutis of scalp

22. Radioiodine therapy
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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 or breastfeeding.
Consider the use of concurrent corticosteroid therapy
with radioiodine or avoidance of radioiodine in patients
with Graves' ophthalmopathy. ( may cause worsening
of ophthalmopathy)
After Radioiodine therapy – mother should stay away
from kids at least for 5 days ( Mother need to Arrange
for a care taker for baby)
Hypothyroidism is inevitable – start Synthroid after
getting TSH level.

23. Surgery
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Especially preferred in :
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Goiter causing obstructive symptoms
Intolerance to thionamides; refusal to take antithyroid drugs or radioactive iodine
Recurrence after a trial of thionamide therapy for Graves’ disease
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%

24. Follow-up
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In pts on long term antithyroid drug therapy
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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.

25. 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
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26. 
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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

27. ANS.A
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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.

28. 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

29. Euthyroid Sick Syndrome

30. Euthyroid Sick Syndrome
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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

31. Q4
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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

32. Key Point
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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.

33. IMP! – AIT
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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.

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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.

35. 
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 druginduced thyroid follicular damage (thyroiditis).

36. Hypothyroidism
Important concepts:
 Hashimato’s
 Lithium induced
Myxedema coma

37. Hashimato’S Thyroiditis
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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

38. Treating Hypothyroidism
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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.

39. 
Ideal Body Weight (men) = 50 + 2.3
( Height(in) - 60 )
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Ideal Body Weight (women) = 45.5 + 2.3
( Height(in) - 60 )

40. Follow up – Treatment adequacy
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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.

41. Follow up – Treatment adequacy
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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

42. 
Advise 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)

43. Lithium Induced
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Li Can cause hypothroidism
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Rx  do not discontinue lithium, Start
levothyroxine and continue lithium therapy.

44. Myxedema Coma
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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.

45. Myxedema coma
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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 :
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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

46. Thyroid Nodule
Approach

47. 
Approach
If thyroid nodule palpable
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FNAC indicated if
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GET TSH First.
If High TSH – suggests cold nodule. Get Thyroid Ultrasound to look for suspicious
features. If no suspicious features, get free T4, TPO Antibodies and Rx as
Hashimatos. If Suspicious features on ultrasound, get FNAC
If TSH low – suggests Hot nodule ( toxic adenoma) but not confirmative ( What if
theres GRAVES and this is a cold nodule?)  so, get RAIU scan next  if COLD
nodule get FNAC. If RAIU scan shows Hot nodule treat with I131 or follow up.
If TSH normal – get Ultrasound next. Do FNAC where indicated ( see below)
Nodule > 10 mm in diameter
On ultrasound if nodule has suspicious features  hypoechoic, microcalcifications,
irregular shape, blurred margin or increased vascularity
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 nodule. ( esply follicular adenoma)

48. 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 Surgery in those cases.
If FNAC is non-diagnostic  repeat FNAC

49. NEJM guidelines

50. Pheochromocytoma

51. Pheochromocytoma
Consider evaluating for Pheochromocytoma in patients with:
 Refractory hypertension
 Hypertension, accompanied by hyperadrenergic spells with:







Family history of familial pheochromocytoma
A genetic syndrome that increases the risk of pheochromocytoma, such as:





Nonexertional palpitations
Diaphoresis
Headache
Tremor
Pallor
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)

52. Pheochromocytoma

Episodic Hypertension is charecterestic but
ORTHOSTATIC HYPOTENSION can be
seen.

Pheochromocytomas are 10% tumors  10%
malignant, 10% bilateral and 10% familial.

53. 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

54. 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)

55. 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 α1adrenergic 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.

56. Primary
Hyperparathyroidism
-Parathyroid Adenomas
-Parathyroid hyperplasia

57. 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;

58. 






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

59. 






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

60. Hyperprolactinemia
-Stress
-Drugs (<100)
-Pituitary Tumors
-Stalk effect
-Hypothyroidism

61. 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!

62. 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)

63. 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.

64. 











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

65. 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

66. Hypoglycemia
Medication induced in Diabetics
Surreptious insulin/ sulfonyl urea abuse
Insulinoma
Treatment


67. INSULINOMA
- Whipples Triad – the symptoms of
hypoglycemia
- C-peptide level.

68. 










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

69. 

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.

70. Glucagonoma
Necrotizing migratory erythema
Octreotide scan

71. 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

72. Polycystic Ovary
Disease

73. 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

74. Cushings Syndrome
Etiology :Adrenal Cushings
Pituitary Cushings
Ectopic Cushings ( Small cell ca)
 Diagnosis : Overnight Low dose (1mg)
dexamethasone suppression test, Urinary 24 hr free
cortisol, High dose (8mg) dexamethasone suppression
test, ACTH level.
CT abdomen if Adrenal cushing suspected
Pituitary MRI if Pituitary adenoma suspected

75. 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

76. Addisons disease/
Adrenal insufficiency
-Random cortisol level
-Cosyntropin Stimulation test – 1hr and 24hr
stimulation tests
-Steroid replacement 
HYDROCORTISOME 100 Q8hrs +
Mineralocortcoid

77. Adrenal Incidentalomas

78. 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)

79. 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

80. 






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

81. 





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

82. 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