Unusual thyroid function tests
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Transcript of Unusual thyroid function tests
Unusual thyroid function tests
• Ross McDougall– Nuclear Medicine Grand Rounds 3/18/2008
Overview of lecture
• “Normal” thyroid physiology• “Normal” patho-physiology• Unusual thyroid function tests
Pituitary
Hypothalamus
Thyrotropin releasing hormone
TRH
Thyrotropin
TSH
Thyroid hormones
Thyroxine T4 (free T4)
Triiodothyronine T3 (free T3)Iodine
trapping
Thyroid physiology
Thyroid patho-physiology
• Increased levels of thyroid hormones– Thyrotoxicosis
• (Hyperthyroidism)• Alternative source of thyroid hormones
» Iagaru and McDougall. J Nucl Med 2007:48:379-389» Mittra et al. J Nucl Med 2008;49:265-278
Patho-physiology
• In almost all situations where Free T4 and or Free T3 are above the normal range…..
• TSH is low and often suppressed (not measurable)– Conversely
• In almost all situations where Free thyroid hormones are low TSH is elevated
Patient 1
Laboratory test 11/15/2007
Free T4 1.5 ng/dl(0.6-1.6)
TSH 11.38 mIU/L(0.4-4.0)
Patient 1
• What could cause this combination of thyroid results?
Patient 1
1) Pituitary tumor secreting TSH2) TSH produced from an ectopic site3) Pituitary resistance to thyroid hormones4) Taking replacement levo-thyroxine
irregularly5) Other causes?6) Falsely elevated thyroid hormone levels
Patient 1: Case history
• 2008 patient is 80 years old• Diagnosed thyrotoxic due to toxic nodular goiter
at age 69 (1997 El Camino)• Free T4 2.4 (0.8-1.8 ng/dl) TSH suppressed• Treated by anti-thyroid medication• 1999 transferred care to Stanford
Patient 1
• Clinically well on antithyroid medication• Mass in left lobe of thyroid and palpable
lymph node• Review of scintiscan
Patient 1
• FNA of left sided nodule HÜrthle cell neoplasm
Patient 1
• Total thyroidectomy– Follicular carcinoma with angio-invasion
• Withdrawal of thyroid hormone for 4 weeks• Low iodine diet during weeks 3 and 4• What tests would you order?
Patient 1
• TSH• Thyroglobulin• Thyroid whole body
scan and uptake
• 9 mIu/l• 85 ng/ml• 23% at 48 hours
• What is unusual about these results?
Patient 1
• Now what?• Ultrasound
– Right lobe 3.2 x 1.2 x 1.1– Left lobe 3.1 x 1.1 x 0.7
• Nodule in right lobe
Patient 1
• Completion of thyroidectomy and I-131 therapy
• Follow-up scan after 1 year negative• Tg undetectable
Patient 1
Laboratory test 11/15/2007 11/26/2007
Free T4 1.5 1.6
TSH 11.3 28.5
Patient 1
12007
112007
112007
1 2008
1 2008
12008
22008
Free T4
1.2 1.5 1.6 1.6 2.1 1.9 1.7
TSH 3.77 11.38 28.53 13.85 6.82 3.82 2.78
Dr Google
15 Reasons Why Your TSH May Be Fluctuating Things to Consider When Your TSH Is Not Stabilized
Patient 1
Patient 1
• Patient was not taking medication regularly
• The TSH value does not respond immediately when there is a change in free thyroid hormones change
Patient 2
• 55 year old employee of Stanford Hospital
• Free T4 0.4 ng/dl (0.6-1.6)• TSH 0.25 mIU/L (0.4-4.0)
• What should be measured?• Free T3 10.2 pg/dl (2.3-4.0)
Patient 2
• Causes for T3 toxicosis– Functioning thyrotoxic nodule– Toxic multinodular goiter– Relapse of Graves’ disease– Taking cytomel (tri-iodothyronine)
• Sometimes this can be a cause of factitious thyrotoxicosis
Patient 2
• This patient has mild T3 toxicosis
Patient 3
• 46 year old man found to have a 5 cm thyroid nodule (1996)
• FNA follicular lesion• Total thyroidectomy: 5 cm follicular cancer• 100 mCi I-131 post operatively• How should he be followed?
Patient 3
• Clinical examination• Measurement of thyroglobulin• Thyroid function tests• Whole-body scan with radio-iodine• Ultrasound
Patient 3
• For 12 years Tg always undetectable (<0.5 ng/ml) irrespective of TSH value
• Primary physician calls patient “your thyroglobulin is 19 go and see your thyroid doctor”
• How do you resolve this?
Patient 3
• 19 is the value of anti-thyroglobulin NOT Tg• One well known clinical laboratory continues to
measure anti-thyroglobulin when thyroglobulin is requested
• Always look at the results yourself !
• However, when thyroglobulin is measured it is important to measure anti-Tg at the same time. Why?
Patient 3
• High Tg was not Tg but antibody to Tg
Patient 4
• 56 year old man– Proven thyroid cancer 3/94– Thyroidectomy in another hospital– I-131 therapy at Stanford– Follow-up scans with radio-iodine negative– Tg undetectable when TSH low, normal, or
high
Patient 4
• Bowel cancer– Neo-adjuvant chemotherapy and radiation
followed by surgery• Severe painful degenerative disease of
spine– Pain management
• Cymbalta
• Atrial fibrillation
Patient 4Free T4 (range 0.8-2.0 ng/dl) TSH (range 0.4-4.0 mIU/L)
2.1 1.2
1.8 9.77
1.5 6.52
2.3 6.49
2.7 3.38
2.3 2.13
1.6 4.88
2.2 1.5
2.4 1.54
Patient 4Free T4 (range 0.6-1.6 ng/dl) TSH (range 0.4-4.0 uU/L)
1.9 0.21
1.2 16.8
1.3 9.0
1.8 2.76
2.0 4.3
1.3 9.08
1.6 7.31
1.8 3.83
Patient 4
• How can a patient have both hyper and hypothyroidism?
• What could cause these disparate values?
TRRXR
HDAHistonedeacetylase activity“turned off”
Histone transacetylase
No T3presentRepressed
T3 presentActivated
TRRXRT3
HAT
1 52 120 370 410 492
Nuclear actions : Thyroid hormone receptors
Transactivation DNA Ligand binding/dimerization
binding
Alpha 1
Alpha 2
Beta 1
Beta 2
• How can a patient be hyper and hypothyroid at the same time?
• The relationship between free T4 and TSH depends on the function of the thyroid hormone receptors
Resistance to thyroid hormone
• Generalized resistance– TSH high– Thyroid hormones
high– No symptoms of
thyrotoxicosis– Goiter– Family history
• Resistance at the pituitary level– TSH high– Free hormones high– Symptoms of
thyrotoxicosis
Patient 4
• The plot thickens
Patient 4
• MRI of brain– Complication of duloxetine [cymbalta
antidepressant in a group of drugs called selective serotonin and norepinephrinereuptake inhibitors (SSNRIs)].
– 6 mm lesion in pituitary– How can we differentiate a TSH secreting
adenoma from resistance to thyroid hormone at the level of the pituitary?
Patient 4
• In pituitary tumor the concentration of TSH alpha -subunits in blood is above normal, as is the ratio of TSH alpha /TSH– TSH alpha 0.6 ng/ml (normal < 1.2 ng/ml)
• TSH level does not respond to changes in thyroid hormone values
Patient 4
• Resistance to thyroid hormone at the pituitary level
Patient 5
• 27 year old papillary thyroid cancer• Treated by thyroidectomy and I-131• Follow-up scan negative• For 2 years Tg always undetectable
(<0.5ng/ml) but she has high values of anti-Tg
Patient 5
• Physician calls her • Tg 24 contact your thyroid doctor• How do you resolve this?
Patient 5
• Look at the results
Patient 5
• In patient 3: the Tg result was actually anti-Tg
• In patient 5: TBG (Thyroxine Binding Globulin) was thought to be Tg
• Always look at the results yourself !– Value was 24 mcg/ml (normal 13.5-30.9)– Repeat Tg was <0.5 ng/ml
Patient 5
• The elevated Tg was not Tg but Thyroid Binding Globulin
Unusual thyroid function tests
• Dogma– Not all dogmas are correct
• Look at the results