2. Objectives
Case based review of Endocrine cases that present in
inpatient and outpatient Internal Medicine
Adrenal : Adrenal insufficiency and incidentalomas
Thyroid: hyper and hypothyroidism, nodules, pearls
PCOS
No disclosures
3. Case #1
36 yo F w/T1DM, hypothyroidism, AI, presents to ED with
extreme fatigue, weakness, abdominal pain, N/V, inability to
take POs including meds
BP 92/54, P 115 lying
72/44, P 138 standing
Labs demonstrate sodium 127, K 5.7, glucose 65, no DKA,
corrected calcium 10.8.
4. Case #1 –Treatment of Adrenal Crisis
Hydrocortisone 100 mg IV x 1, followed by 50 mg IV q 6 hrs
(or continuous infusion 200mg/24 hr)
Volume resuscitation
Once stabilizes, wean steroids to lower doses IV then to PO.
Maintenance doses
HC 15-25 mg/day in 2-3 divided doses
Cortisone acetate 20-35 mg/day in 2-3 divided doses
Prednisolone (3-5 mg/day)
Fludrocortisone required if aldosterone deficiency
JECM 2016;101:364; Endocrine 2017;55:336
5. Adrenal Insufficiency Patient Education
Sick day rules
Steroid emergency card or medical alert identification
Glucocorticoid injection kit and education on use
Follow with Endocrine at least once per year
JECM 2016;101:364; Endocrine 2017;55:336
6. Case #2
62 yo M presents for follow up of SOB/pneumonia, s/p recent
hospitalization. CT scan chest found incidental 2 cm R
adrenal nodule (10 Hounsfield units).
HTN, hyperlipidemia, obesity
HCTZ, ACEi, CCB
BP 144/88, HR 85, BMI 34
PE significant for central obesity, otherwise unremarkable
7. What should you do to evaluate adrenal
incidentaloma?
No further work up is needed
Assess for hyperaldosteronism
Assess for hyperaldosteronism, subclinical cushings
Assess for hyperaldosteronism, subclinical cushings,
subclinical pheo
Assess for subclinical cushings and pheo
8.
9. Evaluation of Adrenal Nodules
Need hormonal evaluation to rule out
Cushings (including subclinical)
MN salivary cortisol, 1 mg dex supp test, 24 hr UFC
Pheo (including subclinical)
Plasma free metanephrines, 24 hr urine metanephrines
Hyperaldo, if pt has HTN or electrolyte abnormalities to suggest
hyperaldosteronism
Renin and aldo screen
Imaging
Low Hounsfield units (<10) reassuring that it is a benign adenoma
If <4cm, looks benign on imaging, and is not producing hormones,
repeat imaging in 3-6 months, then annually for 1-2 yrs
Endocrine Practice 2009 (15): Suppl 1
10. Case #3
40 yo F w/ h/o celiac disease presents w/ complaints of
palpitations and sweating
ROS: Frequent bowel movements, increased appetite, no
change in wt, increase in anxiety. Eyes feel a little more dry
than normal and some grittiness.
FamHx: Maternal aunt with thyroid disorder, s/p RAI
SocHx: +tobacco use, rare Etoh
11. Case #3
PE: HR 110, BP 140/84, BMI 27
HEENT: +lid lag, mild R proptosis, no chemosis, +mild
conjunctival injection
Neck: thyroid mildly enlarged, nontender, no bruit, no
nodules
CV: tachycardic but no M/R/G
Neuro: +fine tremor on exam
Skin: warm, moist, no rash
12. Case #3
You suspect thyrotoxicosis and sendTSH and FT4
TSH <0.01
Ft4 3.9
13. What is the most likely cause of her
symptoms?
Graves’ disease
Thyroiditis
Overactive nodule(s)
Thyroid hormone ingestion
14.
15. How do you determine etiology of
thyrotoxicosis?
Historically, uptake and scan have been first step in evaluation
Two parts:
Uptake (normal 10-30%)
Scan is a picture of thyroid – ie. hot/cold nodules
Uptake will also help identify whether thionamides will work
High uptake states can be treated with antithyroid medications
(thionamides)
16. Hyperthyroid states – High uptake
Graves’ disease
Most common cause in young to middle-aged people
Circulating immunoglobulin attaches toTSH receptor and stimulates
formation of goiter and excessive production of thyroid hormone
Toxic nodular goiter
Multinodular – middle-aged to elderly people.
Probably results from development of autonomy in longstanding goiters
Solitary
Pregnancy – thyroid follicular cells are stimulated by hCG (ie. Molar
pregnancy, choriocarcinoma)
Pituitary resistance to thyroid hormone regulation – rare
TSH secreting pituitary tumor – rare
Thyroid 2016;26:1343-1420
17. NonhyperthyroidThyrotoxic States –
Low uptake
Thyroiditis – liberation of thyroid hormone from the gland
(subacute, silent, postpartum, amiodarone-induced, IFN, IL2,
radiation)
Does NOT respond to thionamides
Treat symptoms w/ BB
Ingestion of pharmacological preparations or food containing
thyroid hormone
Ectopic hormone production from thyroid tissue in abnormal
locations (lingual goiter, struma ovarii, metastatic thyroid
disease)
May see uptake elsewhere with whole body imaging
Thyroid 2016;26:1343-1420
18. Are there other cost effective ways to
determine the etiology?
Thyrotropin receptor antibodies (TRAb) orThyroid Stimulating
Immunoglobulin (TSI)
Positive in Graves’ disease
Indicate that antithyroid medications will work to control thyroid
hormone production
There may be large cost differential b/w the two studies
Other antibodies
Anti-TPO (antimicrosomal)
Anti-thyroglobulin
Can be positive in Graves’ or other thyroid disease (hashimoto’s or
chronic autoimmune thyroiditis)
Less helpful in determining whether antithyroid medications will
work to control thyroid hormone production
19. Back to case #3- Graves’ disease
Given age, gender, h/o personal autoimmune disorder and
family h/o thyroid disease, and physical exam, you suspect
Graves’ disease
CheckTRAb (orTSI)
If positive, can treat with thionamide therapy
If negative, would proceed with uptake and scan to evaluate for
nodule(s) vs. thyroiditis
Case 3TRAb came back positive. How do we treat?
20. Treatment
Beta blockers
Hyperthyroid symptoms are secondary to increased beta
adrenergic receptors
BB help control symptoms of thyrotoxicosis from any cause
Propranolol in high dose can blockT4 toT3 conversion, but most
pts can be treated w/ metoprolol or atenolol on outpt setting
Thyroid 2016;26:1343-1420
21. Thionamides – PTU and methimazole
Patients with high uptake states (Graves, nodules) will respond to
thionamide therapy
Block de novo thyroid synthesis within 1-2 hours
Transported into the thyroid gland where they inhibit both the
organification of iodine to tyrosine residues in thyroglobulin and
the coupling of iodotyrosines
May also inhibit thyroid hormone secretion
PTU also inhibits peripheral conversion ofT4 toT3
Methimazole is first line agent EXCEPT in first trimester of
pregnancy and storm (use PTU)
Thyroid 2016;26:1343-1420
22. Case #3 – Graves’ disease
Pt is started on BB and methimazole 20 mg daily
2-3 wks later, hyperthyroid symptoms are improved
FT4 has come down to 2.6 and BB and methimazole are
continued
23. Patient returns 6 wks later with
complaints of fevers and sore throat
A) Reassure her that she has viral infection
B) Check CBC; hold methimazole until results obtained
C) Stop methimazole and refer to Endocrine
D) Change from methimazole to PTU
24.
25. Side effects of thionamides
Agranulocytosis (ANC <500)
>70% develop agranulocytosis within 60 days, nearly 85% within 90
days
Most pts present with fever 92% and sore throat 85%, thus pt
instructed to call if they have fever and sore throat check WBC
Sheng et al, QJMed 92:455-61, 1999; Nakamura JCEM 98:4776, 2013
Hepatotoxicity
More common with PTU (black box warning) but can occur with w/
methimazole also.
Pt instructed to call if jaundice, pruritus, RUQ pain, scleral icterus,
darkening of urine check LFTs
Anca-associated vasculitis
Pt instructed to call if they develop rash
Thyroid 2016;26:1343-1420
26. Case #4
73 yo AAF w/ h/o hyperthyroidism, s/p discontinuation of
propylthiouracil (PTU) 7 days ago for a planned thyroid
uptake and scan.
Presents w/ a 2 day h/o lethargy, slurred speech and low
grade temp.
N/V on day of admission
27. Case #4 - Physical Exam
HR 120-170 on telemetry, temp 100.5, very lethargic
HEENT: +stare and lid lag; no proptosis or chemosis; sclera anicteric
Neck: thyroid enlarged and nodular, no bruit
CV: Reg rhythm but tachycardic
Resp: Fair respiratory effort, no crackles
Ext: No c/c/e
Neuro: Brisk reflexes, fine tremor present
What are you concerned about?
28. Thyroid Storm – Clinical Presentation
Thyrotoxicosis features are accentuated:
Thermoregulatory dysfunction
Low grade temp temp >104 (sweating can lead to insensible
fluid loss)
Cardiovascular
Tachycardia HR >140; afib; CHF
CNS disturbance
Agitation delirium, psychosis, extreme lethargy seizure
coma
N/V/D jaundice
Precipitant history usually present
Thyroid 2011;21:593; J Int Care Med 2015;30:131
Endocrinol Metab Clin North Am 1993;22:263
29. Atypical presentations
Apathetic hyperthyroidism
May present with apathy, obtundation, cardiac failure
Elderly or those with nonthyroidal illness may not have typical
signs and symptoms of thyrotoxicosis, which can lead to delay
in diagnosis
J Int Care Med 2015;30:131
30. LaboratoryTesting inThyroid Storm
No definitive serumT4 orT3 cutoff to differentiate storm (from
thyrotoxicosis without crisis)
T3 may not appear as high as expected in critically ill patients because
of decreased ability to convertT4 toT3
Common abnormalities: leukocytosis (+/- infection), elevated BUN,
elevated transaminases, hyperbilirubinemia, hypercalcemia (high bone
resorption), hyperglycemia (increased catecholamines and
gluconeogenesis, inhibition of insulin release)
J Int Care Med 2015;30:131
31. Treatment of thyroid storm
Beta-adrenergic blockade
Propranolol PO 60-80 mg Q 4 hrs; Can use IV for faster effect (0.5 to
1.0 mg slow IV push then 1-2 mg at 15-min intervals while monitoring
on telemetry
Alternative (i.e. if borderline BP): Esmolol IV
Antithyroid drug therapy (thionamides)
PTU preferred: +/-Load 500-1000 mg PO, then 200-250
mg q4hr
Methimazole: 60-80 mg/day, in divided doses
Usually PO, but can be suppository or retention
enema Thyroid 2011;21:593, J Int Care Med 2015;30:131;
Thyroid 2006;16:691
32. Treatment of thyroid storm
Iodine blocks release ofT4 andT3 from the thyroid gland and new
hormone synthesis
Inhibit organic binding of iodide toTG in the thyroid (Wolff-Chaikoff
effect)
Transient decrease in thyroid hormone synthesis
Escape phenomenon eventually occurs, usually within 2-4 wks, and
thyroid hormone synthesis resumes
SSKI (saturated solution of potassium iodide) 5 drops (0.25mL or 250
mg) PO every 6 hours OR Lugol’s solution 8 drops every 6 hours
Administer one hour after antithyroid medication has been given
(to prevent iodine from being used as substrate for new thyroid
hormone synthesis)
Would recommend Endocrine consultation in anyone you are
considering SSKI
Thyroid 2011;21:593, J Int Care Med 2015;30:131
33. Treatment of thyroid storm
Glucocorticoids inhibitT4 toT3 conversion
Hydrocortisone +/- 300 mg IV load, then 100 mg IV q 8 hours; alternative is
dexamethasone
Other
Lithium impairs thyroid hormone release and blocks new synthesis
and is alternative if pt has h/o iodine induced anaphylaxis; renal and
neuro toxicity limit usefulness
Cholestyramine binds conjugated thyroid products in gut, thus
promotes excretion and lowers thyroid hormone levels
Physical removal – Plasma exchange removesTBG w/ bound thyroid
hormone. Colloid replacement supplies open binding sites for
circulating free thyroid hormone
Supportive treatment: APAP, cooling blankets, IVF, resp support,
ICU monitoring
Avoid salicylates – Can increase FT4 by decreasing binding toT4 binding
globulin
Thyroid 2011;21:593, J Int Care Med 2015;30:131
34. Definitive therapy for Hyperthyroidism
Graves’ disease
Can treat for 12-18 months with methimazole after which about 1:4
will go into remission and be able to come off methimazole
Continue thionamide long term (less likely to consider this in young
pt)
Radioactive iodine therapy – destroys thyroid tissue, majority end
up needing thyroid replacement
Known to exacerbate thyroid eye disease
Surgical resection – consider if pt has large nodule(s), particularly if
the nodules have concerning features on U/S
MNG or solitary nodule
Won’t go into remission; thus consider definitive therapy with RAI
or surgery
Thyroid 2016;26:1343-1420
35. Case #5
72 yo M w/ h/o CAD, cardiac arrhythmia treated w/
amiodarone x 1 yr, now with thyrotoxicosis (TSH
undetectable, FT4 3 x normal)
Initial evaluation to help determine if the pt has Amiodarone
induced hyperthyroidism type 1 vs. 2
PE: Look for thyroid eye disease, thyroid nodules/goiter
CheckTRAb for underlying Graves’ and U/S to look at
architecture (nodules?) and evidence of thyroiditis
36. Amiodarone induced hyperthyroidism
Type 1
Likely secondary to the
large iodine load on a pre-
existing state of thyroid
disease (Graves’ or
nodules)
Ongoing thyroidal
organification and thyroid
hormone synthesis
May see increased
vascularity on doppler
Thionamide therapy will
help control levels
Type 2
Destructive thyrotoxicosis
from either the iodine or
the drug itself
Thyroid is not making more
thyroid hormone but
releasing the preformed
thyroid hormone
Steroids are best therapy
Thyroid 2016;26:1343-1420
37. Case #5 - AIT
If history, PE and evaluation clearly suggest AIT 1 or AIT2,
treat with methimazole or steroids, respectively
Often, it is challenging to distinguish b/w the AIT1 and AIT2
and/or pt is fairly sick requiring timely intervention
Methimazole 40 mg and prednisone 40 mg daily
If respond quickly, suggests prednisone is the predominant
therapy that is working and thus can taper methimazole down
and potentially off
Amiodarone can affect thyroid for several months
38. Case #6
45 yo F presents with fatigue, wt gain, dry skin/hair
TSH is 40, FT4 0.45
How do you treat her?
Levothyroxine – 1.6 mcg/kg is usual wt based estimation
Start lower if h/o cardiac disease or older pt (ie. 25-50 mcg daily)
Take apart from food or meds (usually morning, but HS will work too)
What ifTSH was 6 w/ FT4 normal?
Could check anti-TPO (antimicrosomal) and if positive, would consider starting
LT4 25 mcg daily if pt had symptoms of hypothyroidism
If subclinical hypothyroidism and +Abs, overt hypothryoidism occurs at rate of
4.3% per year
Endocrine Practice 2012;18:988-1028
39. Case #7
85 yo M with no known thyroid disorder hasTSH 7.0
Symptoms: none
PMHx: CAD, HL, HTN
40. What should you do next?
A) Start levothyroxine 50 mcg daily
B) Start levothyroxine at weight based 1.6 mcg/kg/day
C) Monitor thyroid but do not start levothyroxine
D) Order thyroid ultrasound
41.
42. TSH in elderly pts
RisingTSH is expected with aging
Experts recommend a higherTSH level (>7.5 or 8.5 IU/ml) in
elderly pts
Potential risk of over-replacement with levothyroxine is NOT
outweighed by potential benefit of treating subclinical
hypothyroidism in this population
Thus recommend rechecking TSH in 4-8 wks
JAMA Intern Med 2016;176:1741-1742
43. Case #8
39 yo F with concern that levothyroxine does not work for her
She has been taking thyroid hormone replacement for 4 yrs
with fluctuating levels
TSH 3 months ago was 0.23 with normal FT4
Today:TSH is 7.9 with normal FT4
TSH has been above and below goal over the past few yrs
44.
45. Case #8
Potential causes?
Inconsistent adherence
decreased absorption 2/2 malabsorption (ie. celiac, h/o GI
surgery)
ingestion w/ food/pills or interfering meds
change in estrogen status (pregnancy, menopause, OCPs)
change in formulation (ie. Pt on generic and pharmacy gets
levothyroxine from different manufacturer)
change in requirement due to decreasing residual function or
nonsuppressed endogenous gland function
46. When to think of MyxedemaComa
Symptoms: Hypothermia, bradycardia, hypoventilation, hypotension,
effusions (pericardial, pleural or peritoneal), CNS changes (seizure,
stupor, coma, delay in reflexes)
Three essential elements for diagnosis, confirmed by laboratory
testing
Altered mental status
Coma unusual; generally disorientation, extreme lethargy
Defective thermoregulation
Defective hypothalamic function and inability to produce heat
Precipitating event or illness is common
Pulmonary and urinary tract infections common
If concerned about myxedema coma, need admission.
Endocrine Reviews 2003;4:137
47. Myxedema ComaTreatment
1) IV high dose glucocorticoid therapy
Hydrocortisone 100 mg x 1, then 50 mg IV q 6hr or 100 mg IV q 8 hr
If possible, send cortisol level prior
2) After steroids, give IV thyroid replacement:
ComboT4/T3: Load IV LT4 200-400 mcg followed by 1.6
mcg/kg/day; LoadT3 5-20 mcg followed by 2.5 -10 mcg q 8 hrs. T3
discontinued once pt is stable.
T4 only: Load IV LT4 300-500 mcg bolus to saturate pool, then
50-100 mcg daily.
T3 only: 10-20 mcg, followed by 10 mcg q 6hr for 1-2 days
If IV is not available use PO. Gut wall edema and/or gastric atony
may impair PO absorption.
UpToDate accessed 2/3/18; last updated 6/3/15
JThyroid Research 2011;doi:10.4061/20111/493462
48. Myxedema ComaTreatment
Need ICU monitoring due to risk of respiratory failure and/or
hypotension
Hypotension may be due to volume depletion but may also
respond to thyroid hormone replacement
May need transient vasopressor support
Passive rewarming (blanket) preferred
Active rewarming can cause vasodilation and shock
UpToDate accessed 2/3/18; last updated 6/3/15
49. Thyroid pearls – Common meds that
affect thyroid levels
Heparin (IV, SQ) – falsely elevates FT4 and FT3
IfTSH normal, consider checking total thyroid levels
Estrogen – IncreasesTBG, thus increases thyroid requirements
Pregnancy – Pts need increase in LT4 upon confirmation of pregnancy; multiply
TOTALT4 ref range by 1.5 for pregnancy
Menopause and OCPs change LT4 requirements
Steroids – SuppressTSH; BlockT4 toT3 conversion
Amiodarone – decreases conversionT4 toT3 (thus elevated FT4 w/
low or low-nlT3 and normalTSH)
50. Case #9
66 yo M with swelling of neck. Some hoarseness of voice.
PMHx: HTN, HL, GERD
No known family h/o thyroid disease
PE: 3 cm nodule palpated R lobe thyroid, moves w/
swallowing; appears euthyroid on exam
TSH is normal
IfTSH had been suppressed, would check FT4 and thyroid
uptake/scan to see if nodule if functional
51. What should you do next?
A) Order follow up U/S in 6 months
B) Order follow up U/S in 12 months
C) Order FNA of the nodule
D) Reassure patient that the nodule is small and no further
evaluation is needed
52.
53. Thyroid nodules with normal or elevated
TSH
Very common (~50% of people > 60 yo have them)
4-6% of nodules are malignant
Microcalcification
Irregular borders
Tall shape (height > width)
Extrathyroidal extension
Hypoechogenicity
Prevalence of cancer is higher in children, adults <30 or >60 yrs old, pts w/
h/o head/neck irradiation, pts w/ personal or family h/o thyroid cancer
Concerning symptoms:Voice changes, Dysphagia/Obstructive sx,
Cervical lymphadenopathy
Thyroid 2016;26:1-133.
54. Case #10
30 yo F presents to clinic with complaints of irregular
menstrual cycles and excess hair growth
Menses started age 13, have always been irregular
Hair growth affects chin, abdomen, thighs; requires shaving
and plucking
BMI 28, BP 130/78, mild acne noted
Does she have PCOS? What other diagnoses do you need to
consider?
55. Diagnostic criteria
NIH (1990)
Both criteria required:
Rotterdam (2003)
Two of three required:
Androgen Excess Society
(2006)
Both criteria required:
1) Menstrual
irregularity due to
oligo- or anovulation
2) Clinical or
biochemical
hyperandrogenism
1) Menstrual
irregularity due to
oligo- or anovulation
2)Clinical or
biochemical
hyperandrogenism
3)Polycystic ovaries
(by ultrasound)
1) Hirsutism and/or
biochemical
hyperandrogenemia
2)Ovarian dysfunction –
oligo-anovulation and/or
polycystic ovaries.
All require the exclusion of other causes of irregular menses and
hyperandrogenism (CAH, androgen-secreting tumors, hyperprolactinemia, thyroid
dysfunction)
Zawadzki JK et al. PCOS: current issues in endocrinology and metabolism, vol 4. Boston: Blackwell
Scientific; 235.
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Fertil Steril 2004;81:19-25.
Azziz et al. JCEM 2006;91:4237-4245.
56. Office Evaluation
History
Menstrual cycle history including fertility
Typically chronically irregular menses, sometimes exacerbated by
weight gain
Hyperandrogenism symptoms
Onset, rate of progression
Metabolic risk factors
Family history CVD, HL, or DM2; tobacco use
Physical Exam
BP, BMI, consider waist circumference, signs of insulin
resistance, hair growth, acne, male pattern hair loss
57. PCOS: Diagnosis of exclusion
Exclusion of Other Causes of Symptoms Lab Test
Thyroid dysfunction TSH*
Hyperprolactinemia Prolactin*
Non-classic congenital adrenal hyperplasia Morning 17-hydroxyprogesterone (17-OHP)
Cushing’s syndrome 24 hr urine cortisol, dexamethasone
suppression test, or salivary cortisol
Androgen secreting tumor Total testosterone
DHEA-S
Hypogonadotropic hypogonadism or
primary ovarian insufficiency
FSH, LH, Estradiol
*Order in ALL women with history of irregular menses; **HCG to exclude pregnancy
58. Metabolic Lab Evaluation
Condition Screening test
Impaired glucose tolerance or type 2
diabetes
75g OGTT (fasting, 2 hr glucose level); do at
baseline if obese, or other risk factors (GDM,
fam hx, acanthosis nigricans) and every 2 yrs
after, sooner if clinically indicated
Dyslipidemia Fasting lipid profile, check at baseline and
every two years or sooner if indicated
NAFLD/NASH Consider checking alanine aminotransferase
and aspartate aminotransferase
in women that have other metabolic risk
factors for NASH
Wild et al. JCEM 2010; 95:2038-2049
Setji and Brown Am J Med 2007
59. “MY PCOS”
Metabolic -Assess DM, fatty liver, and CVD risk
-Address lifestyle therapies: nutrition, physical activity
Cycle Control -Assess bleeding pattern and risk for endometrial hyperplasia
-Provide therapies to prevent endometrial hyperplasia
-Hormonal contraception (OCPS, vaginal ring, patch)
-Q 1-3 month progesterone withdrawal
Modified from Setji and Brown. Am J Med 2007
Modified from Setji and Brown. Am J Med 2014
60. “MY PCOS”
Psychosocial -Address body image and eating behaviors; Screen for depression
-Discuss stress management; Provide non-judgmental support
Cosmetic -Discuss use of estrogen-containing OCPs to suppress androgens
-Consider spironolactone 50-100 mg bid for refractory hirsutism or acne
-Discuss laser and electrolysis therapy; enflornithine hydrochloride 13.9% cream
-Discuss topical minoxidil OTC for male-pattern scalp hair loss
Ovulation -Discuss fertility goals and therapies to increase ovulation frequency
-Weight loss, metformin, clomiphene
-Referral to Reproductive Endocrinology for assisted reproductive technologies
Sleep Apnea -Screen for sleep apnea; Refer for sleep study if indicated
Modified from Setji and Brown. Am J Med 2014
61. Summary
Adrenal insufficiency acute and chronic treatment
Adrenal incidentaloma evaluation
Hyperthyroidism and thyroid storm
Hypothyroidism pearls
Thyroid nodules
PCOS evaluation and complications
No disclosures
