Transcript Natural Hormone Replacement Therapy

A Clinical Approach to Thyroid
Insufficiency:
Beyond the TSH/T4 Laboratory
Paradigm
Henry Lindner, MD
Hormonerestoration.com
Conventional Endocrinology:
Missing the Boat
Diagnoses and treats only severe hormonal
disorders caused by disease.
Laboratory Orientation: Uses population
reference ranges to define disease and
treatment
Fails to diagnose if hormone levels are
anywhere within the reference range
Disease/no disease instead of continuum
Blind to the prevalence of moderate
functional and age-related hormone
Clinical
Medicine:
vs. Laboratory
Primacy of Signs and
Symptoms
Notes Relative Levels
Degrees of
Insufficiency
Goal=Optimal Clinical
Response
Primacy of Laboratory
Values
Reference Ranges
Disease/No Disease
Goal=Normalization of
Lab Values
Clinical vs. Biochemical
“It is of special interest that some
patients with severe biochemical
hypothyroidism had only mild clinical
signs, whereas other patients with minor
biochemical changes had quite severe
clinical manifestations.”
Zulewski H, Müller B, Exer P, Miserez AR, Staub JJ. Estimation of tissue
hypothyroidism by a new clinical score: evaluation of patients with various
grades of hypothyroidism and controls. J Clin Endocrinol Metab. 1997
Mar;82(3):771-6.
Tests Cannot Be Used Determine
Dose
Detailed clinical assessments of 148 treated
hypothyroid patients by four experienced
clinicians
“reference ranges for TT4, FT4, and TSH in
patients receiving thyroxine replacement are
considerably different from the conventional
ranges;”
“We consider that biochemical tests of thyroid
function are of little, if any, value clinically in
patients receiving thyroxine replacement.”
“Further adjustments to the dose should be made
according to the patient's clinical response.”
Fraser WD, Biggart EM, O'Reilly DS, Gray HW, McKillop JH, Thomson JA. Are
Clinical Trumps All
“The ultimate test of whether a patient is
experiencing the effects of too much or to
little thyroid hormone is not the
measurement of hormone concentration
in the blood but the effect of thyroid
hormones on the peripheral tissues”
Greenspan FS, Rapoport B. 1991 Tests of thyroid function. In: Greenspan FS, ed.
Basic and clinical endocrinology, 3rd ed. London: Appleton & Lange, Prentice Hall
International; 211.
The Meaning of the Reference
Range
Reference Range=95% of the
population; NOT the optimal range for
any person!
Male testosterone: 250-1000ng/dL
4x!
Female testosterone: 0.0-76ng/dL
!
Free T4: 0.6-1.8g/dL
3x!
Free T3: 2.3-4.2pg/ml
2x!
Far too broad, does not define optimal
Prevalence of Thyroid
Insufficiency
19.7% of the non-diagnosed persons
found to have “subclinical
hypothyroidism”
Kvetny J, Clin Endocrinol (Oxf). 2004 Aug;61(2):232-8
47.5% of blood donors had thyroid
disease by serum testing and
ultrasound.
FT4 RR with normal US was 1.0-1.6
ng/dL
Kratzsch J, Clin Chem. 2005 Aug;51(8):14806
Reference Range View vs.
Physiology
Euthyroid
Ref. Range
View
Signs and
Symptoms
Hypothyroid Optimal Hyperthyroid
Physiological
View
0 Lower Limit
Upper Limit
Serum Hormone Levels
Continuum:
Weight vs. Free T4 Within the
RR
4082 people in
Denmark
Reference Range: 9.8-20.4 nmol/l
J Clin Endocrinol Metab July 2005, 90(7):4019-4024
Continuum: Higher FT4 and
FT3 Levels within the RRs are
Better:
FT3 in upper third of range50%
reduction of incidence of severe
atherosclerosis
Auer J, Clin Cardiol. 2003 Dec;26(12):56973
Lower cholesterol, triglycerides, Creactive protein, homocysteine and
lipoprotein(a)
Lower blood pressure, arterial
dilatation
TSH/T4 RR Nomenclature
Primary hypothyroidism: FT4 with TSH
Central hypothyroidism: FT4 and TSH
Subclinical hypothyroidism: FT4 and TSH
Primary hyperthyroidism: FT4 with TSH
Subclinical hyperthyroidism: FT4 with
TSH
Problems
“Subclinical” could have high or low-RR FT4!
Laboratory, not a clinical classification system!
Ignores actual FT4 levels within RR!
TSH/T4 Thyroidology
The TSH is always right—the perfect
guide for diagnosis and treatment.
Treat with T4 only because T4-to-T3
conversion is always perfect.
The T3 level is irrelevant for diagnosis
or treatment.
Thyroid hormone resistance is rare and
always involve high hormone levels.
Exceptions are rare and can be ignored for practical purposes.
Indicators of Thyroid
Insufficiency
First Rank—Signs and Symptoms
Second Rank—FT4 and FT3 levels
Third Rank—TSH
TSH is indirect—a measure of H-P
activity only, not of thyroid hormone
effects througout the body.
No Caption Found
McDermott, M. T. et al. J Clin Endocrinol Metab 2001;86:4585-4590
The Rotterdam Study (9 ). Analysis of the relationship between subclinical hypothyroidism (SCH) and myocardial infarctions in this study revealed
an attributable risk of 60% (SCH contributed to 60% of the myocardial infarctions in the 124 women who had SCH) and a population attributable
risk of 14% (SCH was involved in 14% of all myocardial infarctions in the entire group of 1149 women). These risks were similar to those
associated with the major recognized cardiovascular risk factors—hypercholesterolemia, hypertension (BP), smoking, and diabetes mellitus. Hak
AE, Pols HAP, Visser TJ, et al. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly
Copyright ©2001 The Endocrine Societywomen: the Rotterdam Study. Ann Intern Med. 2000; 132:270-78.
Thyropause
Endocr Rev. 1995 Dec;16(6):686-715.
Universal Hypothalamic-Thyrotroph
Dysfunction with Aging
120
100
80
60
40
20
0
TSH
B-19yrs
20-39yrs
40-59yrs
60-79yrs
80-99yrs
TSH response to low T4 (2.7-3.2g/dL)
Thyroid. 2007 Feb;17(2):139-44.
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence
study. Arch Intern Med. 2000 Feb 28;160(4):526-34.
The Colorado Thyroid Disease Prevalence Study (2 ). Shown are the age- and gender-specific
Thyroid Hormones T4 T3
Maintain metabolic rate, mood, and energy
Thyroid gland production controlled by
thyroid stimulating hormone (TSH) from
pituitary
T4 (Synthroid, Levoxyl) is the bioidentical
prohormone, must be converted to active T3
in tissues throughout the body.
Thyroid gland makes T4 and T3; We should
restore both hormones
Thyroid hormone resistance can arise by
Thyroid Insufficiency until
Proven Otherwise
Mental fog
Fatigue, depression, anxiety
Cold extremities
Aches and pains
Hair loss, esp. in women
Weight gain
Constipation
Puffy ankles and face
Elevated cholesterol
Diagnosing Thyroid
Insufficiency
Listen to the patient
Always check free T4 and free T3 levels
and consider possibility of hormone
resistance
TSH diagnostic only if elevated--thyroid
gland failure
Don’t overlook moderate thyroid
insufficiency caused by H-P dysfunction
(TSH within RR, hormone levels below
mid-point of RR).
Always consider a trial of adequate thyroid
Symptomatic Patient:
Diagnosis?
TSH
FT4
FT3
0 Lower Limit
Upper Limit
Symptomatic Patient:
Diagnosis?
TSH
FT4
FT3
0 Lower Limit
Upper Limit
Symptomatic Patient:
Diagnosis?
TSH
FT4
FT3
0 Lower Limit
Upper Limit
Symptomatic Patient:
Diagnosis?
TSH
FT4
FT3
0 Lower Limit
Upper Limit
Symptomatic Patient:
Diagnosis?
TSH
FT4
FT3
0 Lower Limit
Upper Limit
The Fatigue, Fibromyalgia, and
Depression Epidemic
Pre-1970s: Docs treated symptoms with
T3 and T4 (desiccated porcine thyroidArmour)
Post-1970s: Docs treat TSH using T4
only!
Doses lowered by 30-50%!
TSH “normalizing” T4 doselow freeT3 ,
weight gain, persistence of symptoms
People with fatigue, fibromyalgia, and
depression often have central thyroid
Thyroid Optimization is
Safe
Eliminating symptoms by raising T4 and
T3 into the upper half of the RR, or
partially suppressing TSH does not
cause:
cardiac abnormalities J Clin Endo Metab. 2000
Jan;85(1):159-64
bone loss Horm Res. 2005;64(6):293-8. Epub 2005 Nov 1
muscle wasting Am J Phys Endol Metab. 2005 Jun;288(6):E106773
In hyperthyroidism, both T4 and T3
levels are above the RR 24hrs/day.
Symptoms are sensitive indicators: hot
Bone Loss
Thyroid hormone increases metabolism
including rate of bone turnover.
If losing bone, will lose bone faster
If gaining bone, will gain bone faster
Most women>30yr old are losing bone
Giving low dose T4 to hypothyroid
women increases bone loss.
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