The 20 th ESEO Congress Alexandria, Egypt May 10-13, 2017 Rapid Interpretation of Thyroid Function Tests: A Case-Based Guide Saleh Aldasouqi, MD, FACE, ECNU Associate Professor of Medicine Chief of Endocrinology Michigan State University East Lansing, Michigan, USA 1
Sweet Memories From ESEO 2014 Geeza Pyramids, Cairo, April, 17, 2014 2
Objectives/Outlines: Cases: Pre-Test Presentation. Review of TFTs; Guide for rapid interpretation of TFTs. Cases: Post-Test Presentation. A personal Thyroid Case. Additional Cases.
Thyroid Gland; Skin Marks Courtesy: Dr. Omar Abu Hijleh
http://www.healio.com/endocrinology/thyroid/news/blogs/%7bc73f26a2-b89a-4781- a6a1-e8045e7664fd%7d/saleh-aldasouqi-md-face-ecnu/blog-the-other-butterfly
Thyroid Disorders Thyroid Dysfunction: Anatomical Disorders: Hyperthyroidism Goiter Hypothyroidism Nodules/Cysts TFTs Cancer 8
Refinements in TSH measurements and ubiquitous lab testing during the past few decades have resulted in a sharp increase in the diagnosis of thyroid dysfunction Ringel and Mazzaferri (1) 1) Journal of Clin Endocr and Metab January 2005
Sounds Familiar?! just blame it on the thyroid The Low Thyroid Function She Was Talking about-- Was: Low TSH: 0.08 10
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How to interpret this TFT Picture..? TSH: 6.1 FT4: 1.0
How to interpret this Thyroid Picture..? How to interpret this Human Picture..?
How to interpret this Thyroid Picture..? How to interpret this Human Picture..? TSH: 6.1 FT4: 1.0
Case 1 AB is a 21 year old woman who is pregnant at 11 weeks of gestation. C/Os: vomiting and anxiety. T4: 13.8; T3: 190. How to interpret these TFTs? What is the diagnosis? Rx:??
Case 2 CD is a 26 year old woman who is pregnant at 10 weeks of gestation. C/Os: vomiting and anxiety. T4: 12.7; T3: 196. How to interpret these TFTs? What is the diagnosis? Rx:??
Case 3 EF is a 43 year old woman seen for second opinion: My family doctor was puzzled by my TFTs, and could not figure them out? Clinically she was not hypothyroid. TSH: < 0.01, T4: Undetectable A/P:??
Case 4 GH is a 21 year old woman with a diagnosis of Graves disease (??) at age 15. S/P RAI ablation, now on L-thyroxine at 250 mcg. P/E: Short, anxious, HR of 110, small firm gland, slow relaxation of DTRs. TSH: 6.4, Free T4: 2.8. A/P:??
Case 5 IJ is a 61 year old woman with fatigue. She is postmenopausal. TSH in January 2005: 6.1; T4 not done If T4 was normal, what is the diagnosis?
Case 5 (Cont d) In the following July: TSH: 1.8, FT4: 0.52. U/S showed simple goiter. Patient was not on thyroid or relevant medications. Further labs: Low FSH, low LH. Now, how to interpret these changing TFTs?
Case 6 KL is a 31 year old woman who was referred by a neurosurgeon for a large pituitary tumor. Prolactin was 82 (upper limit of normal, 28) What test did this neurosurgeon order that urged him to refer the patient to an endocrinologist rather than proceeding with surgery?
Case 7 MN is a 49 year old woman on the medical floor, admitted for puffiness and diffuse effusion: P-P-P. Consultation was made to Endocrinology for thyroid disorder: TSH 4.9. T4 was not ordered. Seen by Nephro; GI; Cardio (nephrotic syndrome, etc, pericardiac or hepatic disease )? Seen by several consultants, residents, & students: Only 2 seasoned (old) physicians suspected a diagnosis of myxedema from patient appearance!? If she is indeed myxedematous: Why is TSH not high?
Discussion Facts about TFTs: Guidelines for appropriate use of TFTs: Caveats in the interpretation of TFTs: Post-Test
Why do we order TFTs? To evaluate thyroid hormonal status (population screening) To monitor T4 replacement/suppression To evaluate goiter/nodules To evaluate effects of medications (e.g. Amiodarone; interferon) In undiagnosed conditions where TFTs may be relevant/altered (e.g. High Prolactin)
Understanding the: TFTs
Tools: Units and Ranges of Measurements: Update TSH: (0.35 4.01) uiu/ml TT4: (4.5 12.50) ug/dl FT4: (0.61 1.37) ng/dl All tests are performed by immunoassay using direct chemiluminometric technology
Tools: Units and Ranges of Measurements: Update TT3: (87 178) ng/dl FT3: (2.8 4.4) pg/ml rt3: (< 30) ng/ml All tests are performed by immunoassay using direct chemiluminometric technology
Thyroid Anatomy, Histology and Physiology Pictures from the internet: Accessed on 10/13/2011, at: http://www.merckmanuals.com/media/professional/figures/mmpe_12end_152_01_eps.gif http://www.colorado.edu/intphys/class/iphy3430-200/image/23-7.jpg
The H-P-T Axis
The H-P-T Axis Pictures from the Internet
Dopamine, Steroids _ + + Depression Heterophil Ab s: HAMA (Adapted)
The Spectrum of Thyroidism M Y X C O M A OH-po S C H - p o Euthyroid S C H - p e r OH-per S T O R M (1) (2) (3) 1) A patient with Myxedema. From: Wolfe Diagnostic Picture Tests in Clinical Medicine [3]. London, 1992 2) A 4 year old, (presumably) euthyroid girl: Malak, a preschooler, 2001 3) A patient with Graves Disease. From: Davidson s Principles and Practice of Medicine. Edinburg, 1999
The Spectrum of Thyroidism M Y X C O M A Overt Hypo thyroid S C H Euthyroid S C H Overt Hyper thyroid T H S T O R M T4 & T3 N o r m a l TSH
Primary Dys-thyroidism M Y X C O M A Overt Hypo thyroid S C H Euthyroid S C H Overt Hyper thyroid T H S T O R M T4 & T3 N o r m a l TSH
Secondary Dys-thyroidism M Y X C O M A Overt Hypo thyroid S C H Euthyroid S C H Overt Hyper thyroid T H S T O R M T4 & T3 N o r m a l TSH
Thyroid hormones affect almost all body systems in both genders Therefore, thyroid disease has wide ranging affects
Manifestations of Dysthyroidism Hypo Hyper T4 & T3 TSH T4 & T3 TSH Thyroid hormones affect almost all body systems
Manifestations of Dysthyroidism Hypo Hyper T4 & T3 TSH T4 & T3 TSH Thyroid hormones affect almost all body systems
Thyroid disease has a wide range of affects The Thyroid The Brain The Liver The Heart The Intestines The Reproductive System The Kidneys
Thyroid disease has wide ranging affects: Hypothyroidism The Liver Increased LDL cholesterol 2 Elevated triglycerides 2 The Intestines Constipation 4 Decreased GI motility 4 The Thyroid The Heart The Brain Depression 1 Decreased concentration 1 General lack of interest 1 Impaired fetal intellectual development 7 Decreased heart rate 3 Increased blood pressure 3 Decreased cardiac output 3 Diastolic dysfunction 3 The Reproductive System Decreased fertility 6 Menstrual abnormalities 6 The Kidneys Decreased function 5 Fluid retention and edema 5
Thyroid disease has wide ranging affects: Hyperthyroidism The Thyroid The Brain Increased adrenergic tone Excitability Hyperkinesia The Liver Increased lipid degradation Negative protein balance Hepatic dysfunction The Intestines Loose stools Increased GI motility Malabsorption The Heart Increased heart rate Palpitations Increased cardiac output Rapid pulse The Reproductive System Decreased fertility Menstrual abnormalities Pregnancy loss The Kidneys Increased GFR function Increased renal blood flow
What TFTs do we need?? TSH. Free T4 is complimentary: While not always needed, it may definitely be needed in some cases? Tests to be obsolete at present: T3 Resin Uptake; Free T4 Index (FTI); T7 Tests not to be done unless needed (?): FT3. Tests not to be done unless (really) needed (?): TT4, TT3 Extremely rarely needed (if ever): rt3
Caveats on TFTs TSH is the most reliable single test! But with some catches/caveats?! Remember that we ultimately treat patients, not numbers!! Remember the endocrine rule of the thumb : Feed back regulation!
Caveats on TFTs Effects of lab artifacts TFTs: HAMA Effects of non-thyroidal diseases on TFTs: S. Euth Effects of medications: Numerous Effects of lab glitches: Ranging from wrong name to all kinds of errors! If on thyroid hormones: Compliance; what formulation; t ½; T3 or T4 or both or mixed: Transitional states: e.g., Post-RAI
TFTs Remember: Slightly elevated TSH can be seen in depression (1). Pulsatile TSH secretions (intra-patient) (2). Recovering states of thyroiditis, sick-euthyroid (3). Heterophil antibodies, and TSH isoforms (3). Various stages of anti-thyroid medications; post-surgical status; compliance with and method of thyroid hormone administration. 1) Brouwer JP. Eur J Endo 2005 2) Cooper D. N E J M 2001 3) Surks M, et al. J A M A 2004
TFTs TSH is a very reliable thyroid test, but one should remember that TSH alone may be deceiving: So, Remember: Secondary hypothyroidism. Heterophil antibodies (HAMA), Lab to Lab variation, TSH isoforms. Resistance to thyroid hormone; TSH-producing tumors; sick euthyroid illness. Effects of medications (steroids, dopamine) on TSH.
Post-Test
Case 1 AB is a 21 year old woman who is pregnant at 11 weeks of gestation. C/Os: vomiting and anxiety. T4: 13.8; T3: 190. How to interpret these TFTs? What is the diagnosis? Rx:??
Case 1 AB is a 21 year old woman who is pregnant at 11 weeks of gestation. C/Os: vomiting and anxiety. T4: 13.8; T3: 190 (Total; so consider units). TSH: < 0.05; Free T4 and Free T3: Elevated-real. How to interpret these TFTs? What is the diagnosis? Rx:??
Case 1 Gestational thyrotoxicosis: HCG acts exactly like TSH; may be associated with Hyperemesis Gravidara. Clinically: Hyperthyroidism, indistinguishable from Graves RAI Scan can not be done; and yet not be helpful (if done by mistake) Rx: None
Case 2 CD is a 26 year old woman who is pregnant at 10 weeks of gestation. C/Os: vomiting and anxiety. T4: 12.7; T3: 196 (Total; units). TSH: Normal; Free T3 and Free T4: Normal How to interpret these TFTs? What is the diagnosis? Rx:??
Case 2 This is a TBG-binding problem (Gestational estrogen). T4 was Total T4!! Total T3 also was high (total). Free T4, T3 should be normal; TSH SHOULD BE Normal Symptoms are misleading (Pregnancy-related) Rx: None
Case 3 EF is a 43 year old woman seen for second opinion: My family doctor was puzzled by my TFTs, and could not figure them out? Clinically she was not hypothyroid. TSH: < 0.01, T4: Undetectable A/P:??
Case 3 The patient is on Tri-iodo-thyronine (Cytomel)! T3 would be most likely high (low TSH). Patient is over-replaced (hyperthyroid)
Case 4 GH is a 21 year old woman with a diagnosis of Graves disease (??) at age 15. S/P RAI ablation, now on L-thyroxine at 250 mcg. P/E: Short, anxious, HR of 110, small firm gland, slow relaxation of DTRs. TSH: 6.4, Free T4: 2.8. A/P:??
Case 4 Resistance to thyroid hormone!! Case published in Endocrine Practice, 2000.
Case 5 IJ is a 61 year old woman with fatigue. She is postmenopausal. TSH in January 2005: 6.1; T4 not done If T4 was normal, what is the diagnosis?
Case 5 IJ is a 61 yr old female with fatigue She is postmenopausal TSH in January 2005: 5.1; T4 not done If T4 was normal, what is the diagnosis? SCH
Case 5 (Cont d) In the following July: TSH: 1.8, FT4: 0.52. U/S showed simple goiter. Patient was not on thyroid or relevant medications. Further labs: Low FSH, low LH. Now, how to interpret these changing TFTs?
Case 5 (cont d) MRI of Pituitary: Diffusely heterogeneous gland; infiltrative/inflammatory. Ultimate diagnosis?
Case 5 (Cont d) In the following July: TSH: 1.8, FT4: 0.52. U/S showed simple goiter. Patient was not on thyroid or relevant medications. Further labs: Low FSH, low LH. Now, how to interpret these changing TFTs?
Case 5 (Cont d) Initial SCH now with low TSH (inappropriate); suspect pituitary dysfunction/hypofunction FSH, LH were normal (age-inappropriate)?! Other hormones normal Dx: Hypophysitis. Started on T4: TFTs normal. MRI is the same, a bit better. Need to monitor other Pituitary hormones.
Case 6 KL is a 31 year old woman who was referred by a neurosurgeon for a large pituitary tumor. Prolactin was 82 (upper limit of normal, 28) What test did this neurosurgeon order that urged him to refer the patient to an endocrinologist rather than proceeding with surgery?
Case 6 TSH (and T4)!!!!!! She had TSH >100; free T4: 0.4. Severe hypothyroidism with compensatory pituitary enlargement. mimicking a pituitary macro-adenoma. Case published as a visual vignette in Endocrine Practice, 2001.
Case 7 MN is a 49 year old woman on the medical floor, admitted for puffiness and diffuse effusion: P-P-P. Consultation made to Endocrinology for thyroid disorder: TSH 4.9. T4 was not ordered. Seen by Nephro; GI; Cardio (nephrotic syndrome, etc, pericardiac or hepatic disease )? Seen by several consultants, residents, & students: Only 2 seasoned (old) physicians suspected a diagnosis of myxedema from patient appearance!? If she is indeed myxedematous: Why is TSH not high?
Case 7 MN is a 49 year old woman on the medical floor, admitted for puffiness and diffuse effusion: P-P-P. Consultation made to Endocrinology for thyroid disorder: TSH 4.9. T4 was not ordered. T4 almost undetectable? Prior RAI ablation for GD. Patient admittedly extremely noncompliant with LT4 Rx. Patient was myxedamatous, and coincidentally had hypopituitarism (Empty Sella): Secondary Hypothyroidism! Lesson: TAKE A BETTER HISTORY? SKILLS OF PHYSICAL EXAM (SPOT DIAGNOSIS)..!
Acknowledgements Jinie Shirey, Department of Medicine, CHM-MSU: Academic assistance. Library Staff: Saint Frances Medical Center (Faith Gruntcheon) and Sparrow (Laura Smith, Steve Kalis, Mike Simmons): Literature search. Residents, fellows, students, colleagues, and MSU and SFMC sonographers: Collaboration and clinical care. Bara and Malak Aldasouqi: IT assistance. Various Web Sites searched via Google and other search engines, for references, images, posted PPT files (Slides-Materials). Dr. Omar Abu-Hijleh (Amman): Slides Most important: All our Patients, Who Are Our Best Teachers!
Normal Thyroid: Whose thyroid is this?
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This is My Nodule? Benign or What!?
Additional Cases
Q: Which is the Original, and which is the Replica..? P SA P SA
The Price is Right?! http://www.1980sflashback.com/1987/economy.asp Source: 1980s Flashback. Date accessed: 4/25/2017.
In the USA, in 1987 In the USA, 2017 In the USA, in 2007
In the USA, in 1987 In the USA, 2017 In the USA, in 2007???? Q: What were the gas prices in 2007..?
An 18 th century physician is examining a patient:?? Courtesey of Mclaren Hospital Library, Flint, Michigan Q: What is he doing?
An 18 th century physician is examining a patient:?? Courtesey of Mclaren Hospital Library, Flint, Michigan Q: What is he doing?
Q: What is this man sleeping on?
Q: Which is the Original, and which is the Replica..? P SA P SA
P SA P SA
The Price is Right?! http://www.1980sflashback.com/1987/economy.asp Source: 1980s Flashback. Date accessed: 4/25/2017.
In the USA, in 1987 In the USA, 2017 In the USA, in 2007???? Q: What were the gas prices in 2007..?
In the USA, in 1987 In the USA, in 2007 In the USA, 2017 A: An Arm and A Leg..!
An 18 th century physician is examining a patient:?? Courtesey of Mclaren Hospital Library, Flint, Michigan Q: What is he doing?
An 18 th century physician is examining a patient: Courtesey of Mclaren Hospital Library, Flint, Michigan A: Inspecting a goiter with a magnifying lens??!!
A: Non-toxic Goiter