autoimmune endocrine disorders endocrine disorders jonathan insel ,md president , arizona chapter...
TRANSCRIPT
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Autoimmune Endocrine
Disorders
Jonathan Insel ,MD
President , Arizona Chapter
American Association of Clinical Endocrinologist
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The Spectrum
• Thyroid: Hashimotos: Goiter
• Hypothyroidism
• Hashitoxicosis
• Postpartum thyroiditis
• Graves disease: Hyperthyroidism
• Thyroid opthalmopathy
• Islet cells: Type 1 DM
• Adrenal: Addisons
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•Parathyroid: Hypoparathyroidism
•Pituitary: Autoimmune hypophysitis
(postpartum 2nd adrenal insufficiency)
• Diabetes insipidus
•Gonads: Premature ovarian failure
• Male hypogonadism
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Autoimmune Disorders Hang Out
Together
• Vitiligo
• Alopecia areata
• Pernicious anemia/atrophic gastritis
• Celiac disease (15% Type 1 DM)
• Lupus,RA,Sjogrens
• MS, Myasthenia
• ITP
• Autoimmune hepatitis,pancreatitis
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• TSH 92
• FREE T4 .7
• + Anti-TPO and Anti-thyroglobulin antibodies
• DTRs: delayed relaxation
• Thyroid enlarged
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THYROID REPLACEMENT
• AVERAGE REPLACEMENT : .7ug/lb.
• 150 lbs. : 150x.7= 100ug or .1mg.
• ELDERLY REQUIRE LESS ( 25-50 ug. less)
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Which of the following interferes with
thyroid absorption?
• Food
• Iron
• Calcium
• Coffee
• All of the above
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What about T3 Rx.?
• Subset of patients may not be able to convert
T4 to T3 efficiently (deiodinase deficiency)
• Can give trial T3 5mcg qd -5 mcg bid(10 mcg
T3 = 50mcg T4)
• ? Armour thyroid – cannot use T4 assay to
follow but can titrate dose with TSH levels
Prefer not to use in the elderly
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30 yo woman on thyroid
replacement calls to inform you she
is 6 weeks pregnant.
TSH 6 months prior: 2.5
.137 mg. T4
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Pregnancy:Estrogen increases TBG
(Thyroid binding globulin)
• Fetus needs adequate T4 from mom
• Goal:TSH < 2.5
• Increase dose by 30 %-2 extra pills/week or
increase dose from .137 to .175/d
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78 yo woman
• TSH 6.8 ( nl.: .4-4)
• Less energy compared to when she was 50
• Normal exam; no goiter.
• 1. Rx with low dose T4?
or
• 2. Observe-repeat TSH in 1 year.
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Subclinical Hypothyroidism
• 10-20% of the population 60 and above have
subclinical hypothyroidism. (TSH 4-10)
Of Those:
• 5% per year progress to overt hypothyroidism
(more commonly if antibody +)
• In 20-50%, the TSH returns to normal
• The rest stay the same
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Subclinical Hypothyroidism –
Development of Ischemic Heart Events
on Rx
Young Patients 40 – 70 years
Older Patients >70
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Subclinical Hypothyroidism – Age Under 70
No T4
T4
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Subclinical Hypothyroidism –
Development of Ischemic Heart Events
•104 of 819 patients treated with thyroxine
•88 of 823 untreated patients
Older Patients over 70 years
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Subclinical Hypothyroidism – Age Over 70
T4
No T4
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•Elderly women (> age 85) with mild TSH
elevation correlates with longevity - in the
municipality of Leidin the Netherlands mild TSH
elevation was associated with lower
cardiovascular and all cause mortality over 4
years (JAMA 2004 Dec1;292(21):2591-9
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Subclinical Hypothyroidism –
Effects of Treatment on GFR
• Decrease in GFR 50% or progression to
ESRD
• 180 patients treated with thyroxine and
129 patients without thyroxine
• Follow-up 34 +/- 24 months
HR for treatment = .28
JCEM Aug/2012
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Duration (years)
Renal event -free survival
Thyroxine
kkkkkkkkkkkkkkkk
No Thyroxine
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Subclinical hypothyroidism: TSH 4-10
•Rx if younger and symptomatic, +antibodies
•T4 may exert a cardio protective effect in
younger folks (<70)
•T4 may protect renal function in individuals
with subclinical hypothyroidism and renal
impairment
•Observation best in elderly
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CARDINAL FEATURES OF GRAVES
DISEASE
• HYPERTHYROIDISM WITH DIFFUSE
HYPERPLASIA OF GLAND
• OPTHALMOPATHY
• DERMOPATHY (PRETIBIAL MYXEDEMA)
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Diagnosing Graves
Clinical
Confirm:FT4,FT3,TSH
TSI (Thyroid stimulating immunoglobulin)
Usually do not need scan/uptake till I-131 RX
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Treatment of Graves
• Methimazole/PTU (prefer methimazole except during pregnancy)
• I-131 Rx. except:
• Pregnancy-always screen before I-131
• Severely toxic/elderly
• Active opthalmopathy
• I-131: inform patient that it will destroy the thyroid and need for long term replacement;suspend antithyroid med prior but continue beta blocker; expect 6-8 weeks to work
• Methimazole : advise patient to call if rash/fever/severe sore throat/joint pains and document
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R.B.
• 22 yo , 3 mos.old daughter
• “out of it”
• Rapid pulse, wt. loss,
hyperventilation, shakiness
• 1/16: Free T4 3.4(.6-1.7)
• TSH .013
• 2/21: P 68
• Thyromegaly
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RB
• Free T4 .37
• TSH 30.8
• ANTI-TPO 6681
• I-131 UPTAKE .6%
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Serum TSerum T44 Serum TSHSerum TSH Thyroid RAIUThyroid RAIUIncreasedIncreased
NormalNormal
DecreasedDecreased
DeliveryDeliveryand 9 Monthsand 9 MonthsPostpartumPostpartum
00 11 22 33 44 55 66 77 88 99
HyperthyroidHyperthyroid HypothyroidHypothyroid EuthyroidEuthyroid
Clinical Course of Silent,
Postpartum, and Subacute
Thyroiditis
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Subclinical hyperthyroidism:
usually multinodular goiter in
elderly
TSH < .1, nl FT4/FT3
Risk Atrial Fibrillation 3xs normal
(From 11% to 28%)
Risk of bone loss
Rx:Antithyroid Rx,Beta blockers,I-131
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Type 1 DM: Autoimmune
destruction of islet cells
• Clinically:Polys,weight loss,visual blurring,
• Ketones- + urine/risk DKA
• Confirm by measuring C-peptide and antibodies:
• Anti-GAD (glutamic acid decarboxylase)
• Anti-insulin
• Anti-islet cell
• Can come on anytime in life-LADA-Latent autoimmune diabetes of adults
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Rx DM1
• MDI- Basal: Glargine or Detemir
• Premeals: Aspart,Glulisine,Lispro
• Insulin pumps
• Continuous glucose monitoring
• Dexcom- G4
• Medtronics- Veo-suspends infusion for
2 hours at a low BS threshold
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Basal/Bolus Insulin Absorption Pattern With
Standard Insulin Preparations
Skyler J. Kelley’s Textbook of Intern Med. 2000.Skyler J. Kelley’s Textbook of Intern Med. 2000.
Pla
sm
a In
sulin
(µ
U/m
L)
Pla
sm
a In
sulin
(µ
U/m
L)
TimeTime4:004:00 8:008:00 12:0012:00 16:0016:00 20:0020:00 24:0024:00 4:004:00 8:008:00
75
50
25
0
75
50
25
0
NPH/LenteNPH/Lente
LunchLunchBreakfastBreakfast DinnerDinner
GLARGINE/PUMP
LisproLispro LisproLispro LisproLispro
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• VEO
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Islet cell transplant
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35 yo physician
• AGE 12 TYPE 1 DM
• 18 MOS AGO: BLOATING/DIARRHEA-
Rxed FLAGYL
• 1 MOS PRIOR: INCREASE BLOATING/
DIARRHEA ;HYPOGLYCEMIA
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50 yo woman C/O fatigue
• Since 1999 spells of extreme dizzinesss,fuzziness,
and nausea
• Dxed:anxiety-Valium,Compazine
• Dxed: Menieres,Vestibular migraine
• Past year bedridden
• Cannot stand for any interval; lightheaded when she
walks
• Weight loss: 147-124 now at 130 lbs
• Amenorrhea past 2months
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DT
• BP 108/80 supine and 78/60 standing
• Thyroid:mild firmness
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Addisons
• Fatigue, weight loss, orthostatic lightheadedness, salt craving, hyperpigmentation, nausea & vomiting, failure to thrive, hypoglycemia
• Dx: Lytes ( low Na and elevated K) ,
• AM cortisol , ACTH, +anti-adrenal antibodies
• Cortrosyn stimulation test:
250 mcg Cortrosyn: 0,30 and 60 minute Cortisols
Failure to stimulate >20 mcg/dl
•
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Rx of Addisons
• Hydrocortisone 15-25 mg/d in split dosages
Alternatives: Prednisone: 5-7.5 mg/d
Dexamethasone : .25-.5 mg/d
Fludrocortisone:.05-.1 mg/d
? DHEA in women
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Patient with Addisons calls with fever
and myalgias
• Double the glucocorticoid dose
• If N/V or signs of crisis-100 mg Solu-cortef or
• 4 mg Dexamethasone IM; always have
injectable steroid available
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Patient with Addisons undergoing
surgery
Solucortef: 50-100 mg pre and post op
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55 yo
• DM1: 8yrs ago-insulin
• Hx thyroidectomy for benign nodules-T4
• Cholecystectomy 6 month prior-since N/V;
60 lb wt. loss,weakness
BS 600 , non ketotic,K 6.0
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LB: Autoimmune Polyglandular
Syndrome Type2 (Schmidt’s
syndrome)• Addisons - + anti-adrenal antibodies
• Hypothyroidism –prior thyroidectomy for
benign goiter- +anti-thyroid peroxidase
• Type 1 DM- + anti-GAD
• + anti –parietal cell antibody
B-12: 885
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KM
• Addisons
• Hypothyroidism
• Alopecia totalis
• Vitiligo
• Psoriasis
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The Holy Grail
• Immune tolerance : neutralizing the immune
assault to self antigens-reprogramming the
immune response to accept ourselves
• Understanding the triggers