Showing posts with label TSH. Show all posts
Showing posts with label TSH. Show all posts

Sunday, November 13, 2016

Dr Antonio Bianco Rattles Cages in Mainstream Endocrinology by Jeffrey Dach MD

Dr Antonio Bianco 
Rattles Cages in 
Mainstream  Endocrinology

by Jeffrey Dach MD
 
Dr Antonio Bianco asks a very important question, “Does a normal serum TSH indicate adequate treatment in patients given levothyroxine (T4-only) medication?” His answer, published in the Oct 2016 Endocrinology and Metabolism, may rattle a few cages, and is in agreement with what we have been writing for many years now.

Dr Antonio Bianco found levothyroxine (T4) treated patients had difficulty converting T4 into T3, were more likely to be overweight, taking anti-depressants and statins, and had low thyroid symptoms in spite of levothyroxine. Dogmatically clinging to the TSH reference range, and to T4 levothyroxine as the only acceptable thyroid medicine is the error and tragedy of mainstream endocrinology. Dr Bianco’s report has freed endocrinology from the shackles of this false medical dogma. We have written for many years that natural dessicated thyroid (Naturethroid from RLC labs) is a better choice compared to T4 monotherapy with levothyroxine, and that in some cases, suppression of TSH below the reference range is required for relief of symptoms.

Antonio Bianco MD, is an endocrinologist and past president of the American Thyroid Association (ATA) at Rush Medical School in Chicago.  His article is entitled :  Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine MonotherapyLeft image Dr Antonio Bianco Courtesy of the NIH.


Dr Antonio Bianco studied 469 patients treated with levothyroxine (T4 only) for hypothyroidism, and compared to normal controls.  He found:

1) Levothyroxine (T4) treated patients ” had higher serum free T4 and lower serum free T3 than healthy or matched controls.”
My comment: T3 (tri-iodothyronine) is the active thyroid hormone, so a lower serum T3 means these patients are having difficulty converting T4 into T3 and may be suffering from low thyroid symptoms in spite of  levothyroxine (T4).

2) Levothyroxine treated patients were more likely to be overweight despite consuming less calories,
My comment: Weight gain is a common symptom of the low thyroid condition caused by slow metabolic rate, and failure to convert calories to energy.  Instead, consumed calories are stored up as weight gain.
3) Levothyroxine patients were more likely to be taking anti-depressants, and anti-cholesterol (statin) drugs compared to matched controls.”  
My comment: Lack of energy, fatigue and depression are common symptoms of the low thyroid condition, all relieved by providing adequate thyroid dosage.  Many publications, including the Hunt Study, showed that elevated serum cholesterol is a symptom of the low thyroid condition.  Providing a higher dosage of thyroid medicine is the correct treatment. This will suppress the TSH,  reduce serum cholesterol and prevent heart attacks.   Instead of giving thyroid medicine, the proper medication, the conventional doctor will commonly prescribe a statin anti-cholestrol drug which will reduce serum cholesterol without treating the low thyroid condition.  This is the terrible tragedy and error of mainstream medicine.

Dr Bianco Speaks Out

Dr Antonio Bianco’s study reports that levothyroxine dosage based on the TSH reference range does NOT necessarily provide symptom relief for many patients.(15-17)  That’s because dosage based on TSH range may be inadequate, and higher dosage with suppression of TSH may be needed for complete relief of low thyroid symptoms.

Suppression of TSH May be Needed For Symptom Relief

We have found that suppression of TSH below the reference range is frequently needed for complete symptom relief in the low thyroid patient.  Although endocrinology dogma  opposes TSH suppression, in actuality, endocrinologists commonly suppress the TSH long term with thyroid medicine in two groups of patients, the post thyroidectomy patients and the thyroid nodule patients.  Numerous published studies show no adverse effects of TSH suppression in both groups.  For more on this see: TSH Suppression Benefits and Adverse Effects

The Low Thyroid Condition – Case Report

Thyroid Gland in NeckMary is a 57 year old female with chronic fatigue, dry, brittle hair, dry skin, muscle aches and pains, and depression, all obvious symptoms of a low thyroid condition. Mary has been to a number of endocrinologists, primary care doctors and even sought advice from her hair stylist. Her latest doctor prescribed a thyroid pill called Levothyroxine (50 mcg) which has done little to relieve her symptoms. In addition, she has depression, and her psychiatrist prescribed an SSRI antidepressant, called Zoloft. She also takes Xanax for bouts of anxiety and insomnia. Mary came into the office frustrated with her conventional medical treatment which was not helping her.

Routine Thyroid Panel

Our routine evaluation includes a full medical history, physical examination and lab panel. Mary’s baseline lab panel showed a TSH of 5.2, a Free T3 of 260 and a Free T4 of 1.4. TPO antibodies were very elevated (1,100) indicating Hashimoto’s Thyroiditis. Her spot urinary Iodine level was 47 mg/dl indicating iodine deficiency (based on World Health Organization Guidelines).

Switching from Levothyroxine to Natural Thyroid

ThyroidRadionuclideScanThyroxineMary was switched from Levothyroxine to Naturethroid from RLC labs and within a week reported improvement in clinical symptoms. Six weeks later Mary’s Naturethroid dosage was gradually increased to Two and a Half Tablets every day (Using one grain tablets of 65 mg each) . Mary reports improvement. She has tapered off her antidepressants, as she no longer needs them.

Going to the OB/Gyne

Ten weeks later, Mary goes to see her OB Gyne doctor for her annual Pap smear and pelvic exam which included a TSH blood test, with a low result (0.1 which is below the reference range RR).

Her OB/Gyne doctor looks at the TSH test result and tells Mary she is taking too much thyroid medicine and needs to cut back. Mary then calls me at my office to relay this information. Two doctors are telling her different things and Mary doesn’t know who to believe. This scenario plays out in my office with a different patient each week.

The reality is that Mary is on the proper dosage of thyroid medication, and we expect to see a low or suppressed TSH result when this occurs.

In Part One of this series, we discussed how treatment of the low thyroid condition with natural thyroid is superior to Levo-thyroxine (also called Synthroid a T4 only medication).

Pig Natural Desiccated Thyroid Naturethroid RLC LabsIn our office we use Nature-throid from RLC labs. (Disclosure: NONE, I have no financial relationship with RLC labs, the manufacturer of Nature-Throid NDT – natural dessicated thyroid pills) .
Natural Thyroid which contains both T3 and T4 is a more robust and safer thyroid medication when compared to T4 only medications such as levothyroxine and Synthroid. This is my assessment, based on 10 years of clinical experience prescribing Naturethroid. In addition, we have found that patients who have converted from Synthroid to Natural Thyroid are much happier with their treatment program. The mainstream medical literature is also in agreement.

In part one of this series, we also discussed how the TSH test is not a reliable indicator of adequacy of treatment.(2) In other words, when the patient is taking the proper dosage of natural thyroid medication with complete relief of symptoms, the TSH will typically fall below the lab reference range, also called a suppressed TSH.

In other words, the TSH will be quite low, and this will disturb the mainstream clinician who mistakenly believes the patient is taking too much thyroid medication. The issue can be settled simply by running a Free T3 test which will show that the Free T3 in the normal range, thus excluding any possibility of a “hyperthyroid state”. Unfortunately, most conventional docs do not have the knowledge to order a free T3 test, and have limited understanding of the thyroid patient.

Suppressive Dose Needed –The TSH Test is Not a Reliable Monitor
Many patients do quite well on Synthroid. However about 20% (one fifth) of patients on T4 only medications like Synthroid do not do well, and have continued symptoms of a low thyroid condition.(3) Why is that? A miniscule amount of T4 medication such as 50-88 mcg of Levothyroxine may be sufficient to drive down the TSH, and the endocrinologist will then consider treatment dosage adequate. It is not adequate. This is explained by Dr D.S. Oreilly in his articles (4-5), and by Dr. Henry Lindner in his detailed article highlighting why TSH suppression below the lab reference range is needed for adequate treatment for the low thyroid condition. (6)

JapanNuclearAccidentIodineFukushimapowerplant1Japan in Agreement
In agreement is another article, this time from the Center for Excellence in Thyroid Care, Kuma Hospital, Japan in which the authors state that :
“TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy “(9),
Again, knowledgeable physicians are finding that TSH suppression below the lab reference range is required for adequate treatment of the low thyroid condition. In this Kuma Hospital study, doctors found TSH-suppressive doses of Synthroid were needed in post-thyroidectomy patients to achieve the same normal Serum T3 levels which were present on pre-operative labs.

Natural Thyroid
When Natural thyroid medication is used, and the dosage gradually adjusted upwards from 1/2 tab daily to the maintainance dose of two to three of the One Grain (65mg) Tabs daily (usually done over 6 weeks), the lab panel at this time will typically show a TSH which is below the normal reference range, and a free T3 which is in the upper end of the normal range 350-420. The low TSH is to be expected, is not disturbing, and is not indicative of a hyperthyroid state.

Why Has Endocrinology Mismanaged  the Low Thyroid Condition for Fifty Years?
money1The answer is obvious. Follow the money trail. Synthroid is the fourth most prescribed drug in America with 70 million prescriptions. Abbot labs, the makers of Synthroid, uses the massive profits to finance and fund Endocrinology Groups and Societies, their meetings, and clinical research grants. They also fund the key opinion leaders to give lectures at meetings in support of Synthroid and the TSH test. This is all done in spite of the obvious clinical inferiority of T4 only medications such as levothyroxine, and the unreliability of the TSH test to monitor adequacy of treatment. For many decades now, mainstream endocrinology has been completely corrupted by huge cash infusions from Big Pharma. Welcome to America. It’s a great country.

Disclosure: NONE: I have no financial relationship with the makers of natural desiccated thyroid tablets.

Articles With Related Interest

TSH Suppression Benefits and Adverse Effects

New Study Shows Natural Thyroid Better than Synthetic

Ann Nicole Smith and Hypothyroidism
Why Natural Thyroid is Better than Synthetic Part One
Why Natural Thyroid is Better Part Two
The TSH Reference Range Wars – Part One
TSH Wars, Part Two

Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
www.jeffreydachmd.com
www.drdach.com
www.naturalmedicine101.com
www.bioidenticalhormones101.com
www.truemedmd.com

Links and References

1) http://www.scielosp.org/scielo.php?pid=S0042-96862002000800007&script=sci_arttext
Bulletin of the World Health Organization
Bull World Health Organ vol.80 no.8 Genebra Aug. 2002

dx.doi.org/10.1590/S0042-96862002000800007
Determining median urinary iodine concentration that indicates adequate iodine intake at population level by François Delange,1 Bruno de Benoist,2 Hans Bürgi,1 & the ICCIDD Working Group3

2) www.ncbi.nlm.nih.gov/pubmed/16416346
TSH may not be a good marker for adequate thyroid hormone replacement therapy. Wien Klin Wochenschr. 2005 Sep;117(18):636-40. Alevizaki M, Mantzou E, Cimponeriu AT, Alevizaki CC, Koutras DA. Endocrine Unit, Dept Medical Therapeutics, Alexandra Hospital, Athens University School of Medicine, Athens, Greece.
The objective of this study was to evaluate parameters of thyroid function and indices of peripheral thyroid hormone action (such as SHBG) in patients whose hypothyroidism was considered well controlled under current criteria. 85 – Eighty-five patients with T4-treated hypothyroidism, 28 of whom had athyria, were compared with 114 normal individuals with the same TSH levels. T3 levels were significantly lower in hypothyroidism although mean T4 and fT4 levels were significantly higher. Furthermore, mean SHBG levels were significantly lower in hypothyroidism independently of age. The difference remained when stricter criteria for adequate treatment were applied (TSH < 2.5 microgU/ml). Significant negative correlations were found between logTSH and T3. The slopes of the regression lines of T3 to TSH were significantly different in the control group and the hypothyroid group: thus, for the same TSH levels, T3 levels were lower in the hypothyroid group. “We conclude that patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver. TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues. The co-administration of T3 may prove more effective in this respect,“ provided novel suitable preparations are developed. Until this is accomplished, substitution in hypothyroidism should aim at low normal TSH, to ensure normal T3 levels.
2011

3) www.ncbi.nlm.nih.gov/pmc/articles/PMC3148220/ .free full text ….
www.ncbi.nlm.nih.gov/pubmed/21829633
Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients (normal TSH). Dr Damiano Gullo MD – Endocrine Unit, University of Catania Medical School, Catania, Italy PLoS ONE 6(8): Published: August 1, 2011
20% of patient on Synthroid (T4) will have abnormal T3/T4 ratios because they are unable to convert T4 to T3. I say: They need a more physiologic treatment such as natural dessicated thyroid. “More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion.”
Context- Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients.
Objective – To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback. Setting – Academic hospital.Patients- 1,811 patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls.
Measurements – TSH, FT4 and FT3 concentrations by immunoassays.
Results- FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals.
The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients.
Conclusions- Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients.
2010
4) www.ncbi.nlm.nih.gov/pubmed/20584231
Thyroid hormone replacement: an iatrogenic problem.
Int J Clin Pract. 2010 Jun;64(7):991-4. Dr O’Reilly DS. Department of Clinical Biochemistry, Royal Infirmary, Glasgow, UK.
Abstract Thyroid hormone replacement is one of the very few medical treatments devised in the 19th century that still survive. It is safe, very effective and hailed as a major success by patients and clinicians. Currently, it is arguably the most contentious issue in clinical endocrinology. The current controversy and patient disquiet began in the early 1970s, when on theoretical grounds and without proper assessment, the serum thyrotropin (TSH) concentration was adopted as the means of assessing the adequacy of thyroxine replacement. The published literature shows that the serum TSH concentration is a poor indicator of clinical status in patients on thyroxine. The adequacy of thyroxine replacement should be assessed clinically with the serum T3 being measured, when required, to detect over-replacement.
1986
5) www.ncbi.nlm.nih.gov/pmc/articles/PMC1341585/
Br Med J (Clin Res Ed). 1986 September 27; 293(6550) full text
Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement? W D Fraser, E M Biggart, D S O’Reilly, H W Gray, J H McKillop, and J A Thomson
To establish their role in monitoring patients receiving thyroxine replacement biochemical tests of thyroid function were performed in 148 hypothyroid patients studied prospectively. Measurements of serum concentrations of total thyroxine, analogue free thyroxine, total triiodothyronine, analogue free triiodothyronine, and TSH thyroid stimulating hormone, made with a sensitive immunoradiometric assay, did not, except in patients with gross abnormalities, distinguish euthyroid patients from those who were receiving inadequate or excessive replacement. These measurements are therefore of little, if any, value in monitoring patients receiving thyroxine replacement. To stop doing thyroid function tests in these cases would result in considerable savings nationally in the cost of reagents in laboratories using commercial kits.
Article By Henry Lindner MD
6) hormonerestoration.com/files/TSHWrongtree.pdf
Against TSH-T4 Reference Range Thyroidology: The Case for Clinical Thyroidology Henry H. Lindner MD1
The current reliance upon the TSH to both detect hypothyroidism and direct its treatment is illogical and ineffective. Hypothalamic-pituitary function is modified by many known and unknown factors, and is known to deteriorate with age. Even if one could know that a person’s hypothalamic-pituitary response is perfect, one cannot assume that the TSH response to once-daily oral thyroid replacement is identical to the response to continual thyroidal hormone production. The TSH level is only a measure of the hypothalamic-pituitary response to thyroid hormones. It is neither a test of free thyroid hormone levels nor of thyroid hormone effects throughout the body. It is useful for determining the cause of hypothyroidism; not for diagnosing or treating it. The most reliable serum tests of thyroid hormone sufficiency are free T4 and free T3, but their broad laboratory reference ranges are neither optimal nor treatment ranges, and there are marked individual variations. Ultimately, both the diagnosis and treatment of hypothyroidism must be clinical.
7) www.ncbi.nlm.nih.gov/pubmed/11201857
Thyroid. 2000 Dec;10(12):1107-11. Is excessive weight gain after ablative treatment of hyperthyroidism due to inadequate thyroid hormone therapy?
Tigas S, Idiculla J, Beckett G, Toft A. Source Endocrine Unit, Royal Infirmary, Edinburgh, Scotland.
Abstract There is controversy about the correct dose and form of thyroid hormone therapy for patients with hypothyroidism. Despite restoration of serum thyrotropin (TSH) concentrations to normal, many patients complain of excessive weight gain. We have compared weight at diagnosis of hyperthyroidism with that when euthyroid, evidenced by a stable, normal serum TSH concentration, with or without thyroxine (T4) replacement therapy, in patients treated with an 18-month course of antithyroid drugs (43 patients), surgery (56 patients), or 13I (34 patients) for Graves’ disease. In addition, weights were recorded before and after treatment of 25 patients with differentiated thyroid carcinoma by total thyroidectomy, 131I, and long-term T4 suppressive therapy, resulting in undetectable serum TSH concentrations. Mean weight gain in patients with Graves’ disease who required T4 replacement therapy following surgery was significantly greater than in those of the same age, sex, and severity of hyperthyroidism rendered euthyroid by surgery (3.9 kg) (p < 0.001) or at the end of a course of antithyroid drugs (4.1 kg) (p < 0.001). Weight gain was similar in those requiring T4 replacement following surgery or 131T therapy (10.4 versus 10.1 kg). In contrast, ablative therapy combined with suppression of TSH secretion by T4 in patients with differentiated thyroid carcinoma did not result in weight gain. The excessive weight gain in patients becoming hypothyroid after destructive therapy for Graves’ disease suggests that restoration of serum TSH to the reference range by T4 alone may constitute inadequate hormone replacement.
8) www.ncbi.nlm.nih.gov/pmc/articles/PMC143526/
BMJ. 2003 February 8; 326(7384): 311–312. PMCID: PMC143526 full text free
Serum thyroid stimulating hormone in assessment of severity of tissue hypothyroidism in patients with overt primary thyroid failure: cross sectional survey Christian Meier, senior registrar in endocrinology, Peter Trittibach, clinical research fellow, Merih Guglielmetti, statistician, Jean-Jacques Staub, emeritus professor of endocrinology, and Beat Müller, head of division Division of Endocrinology, Department of Medicine, University Hospital, CH-4031 Basle, Switzerland
We found no correlations between the different parameters of target tissues and serum TSH. Our findings are in accordance with a cross sectional study showing only a modest correlation between TSH and the percentage of positive hypothyroid symptoms4 and data showing discordant responses between the pituitary and peripheral target tissues in patients treated with l-triiodothyronine.5 We assume that secretion of TSH is driven by maximal stimulation, with no further increase occurring with greater severity of hypothyroidism. Therefore, the biological effects of thyroid hormones at the peripheral tissues—and not TSH concentrations—reflect the clinical severity of hypothyroidism. A judicious initiation of thyroxine treatment should be guided by clinical and metabolic presentation and thyroid hormone concentrations (free thyroxine) and not by serum TSH concentrations.
TSH suppression required to achieve good result with Synthroid
9) http://www.eje-online.org/content/167/3/373.abstract
TSH-suppressive doses of levothyroxine are required to achieve preoperative native serum triiodothyronine levels in patients who have undergone total thyroidectomy by Mitsuru Ito,Akira Miyauchi,Shinji Morita,Takumi Kudo,Eijun Nishihara, Minoru Kihara,Yuuki Takamura,Yasuhiro Ito, Kaoru Kobayashi, Akihiro Miya, Sumihisa Kubota and Nobuyuki Amino from the Center for Excellence in Thyroid Care, Kuma Hospital, 8-2-35, Shimoyamate-Dori, Chuo-Ku, Kobe-City, Hyogo 650-0011, Japan
Objective Thyroidal production of triiodothyronine (T3) is absent in patients who have undergone total thyroidectomy. Therefore, relative T3 deficiency may occur during postoperative levothyroxine (l-T4) therapy. The objective of this study was to evaluate how the individual serum T3 level changes between preoperative native thyroid function and postoperative l-T4 therapy.
Methods We retrospectively studied 135 consecutive patients with papillary thyroid carcinoma, who underwent total thyroidectomy. Serum free T4 (FT4), free T3 (FT3), and TSH levels measured preoperatively were compared with those levels measured on postoperative l-T4 therapy.
Results Serum TSH levels during postoperative l-T4 therapy were significantly decreased compared with native TSH levels (P<0.001). Serum FT4 levels were significantly increased (P<0.001). Serum FT3 levels were significantly decreased (P=0.029). We divided the patients into four groups according to postoperative serum TSH levels: strongly suppressed (less than one-tenth of the lower limit); moderately suppressed (between one-tenth of the lower limit and the lower limit); normal limit; and more than upper limit. Patients with strongly suppressed TSH levels had serum FT3 levels significantly higher than the native levels (P<0.001). Patients with moderately suppressed TSH levels had serum FT3 levels equivalent to the native levels (P=0.51), and patients with normal TSH levels had significantly lower serum FT3 levels (P<0.001).
Conclusions Serum FT3 levels during postoperative l-T4 therapy were equivalent to the preoperative levels in patients with moderately suppressed TSH levels. Our study indicated that a moderately TSH-suppressive dose of l-T4 is required to achieve the preoperative native serum T3 levels in postoperative l-T4 therapy.
10) full text
http://content.karger.com/ProdukteDB/produkte.asp?Doi=339447
Translational Thyroidology / Review
Thyroid Hormone Replacement Therapy: Three ‘Simple’ Questions, Complex Answers
Antonio C. Bianco, Sabina Casula from the Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine, Miami, Fla., USA
Eur Thyroid J 2012;1:88-98
11) http://www.ncbi.nlm.nih.gov/pubmed/22593590
http://jcem.endojournals.org/content/97/7/2256.short
J Clin Endocrinol Metab. 2012 Jul;97(7):2256-71. doi: 10.1210/jc.2011-3399. Epub 2012 May 16.
Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism? Biondi B, Wartofsky L. Department of Clinical and Molecular Endocrinology and Oncology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.
Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic.
We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action.
The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients.Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.
12) http://www.eje-online.org/content/early/2012/11/26/EJE-12-0819.short
Is Pituitary Thyrotropin an Adequate Measure Of Thyroid Hormone-Controlled Homeostasis During Thyroxine Treatment? by Rudolf Hoermann, John E M Midgley, Rolf Larisch and Johannes W Dietrich
Objective. In recognition of its primary role in pituitary-thyroid feedback, thyrotropin (TSH) determination has become a key parameter for clinical decision-making. The present study evaluates the value of TSH as a measure of thyroid hormone homeostasis under T4 therapy.
Design,
Methods. We have examined the interrelationships between free triiodothyronine (FT3), free thyroxine (FT4) and pituitary TSH by means of 1) a retrospective analysis of a large clinical sample comprising 1994 patients either untreated or on varying doses of L-T4 and 2) independent mathematical simulation applying a model of thyroid homeostasis, together with a sensitivity analysis.
Results. Over a euthyroid to mildly hyperthyroid functional range, we found markedly different correlation slopes of log TSH versus FT3 and FT4 between untreated patients and L-T4 groups. Total deiodinase activity (GD) was positively correlated with TSH in untreated subjects. However, GD was significantly altered and the correlation lost under increasing L-T4 doses. 95% confidence intervals for FT3 and FT4, when assessed in defined TSH concentration bands, differed significantly for L-T4-treated, compared to untreated patients. Higher doses were often needed to restore FT3 levels within its reference range. Sensitivity analysis revealed the influence of various structural parameters on pituitary TSH secretion including a preeminent role of pituitary deiodinase type 2.
Conclusion. The data reveal disjoints between FT4-TSH feedback and T3 production that persist even when sufficient T4 apparently restores euthyroidism. T4 treatment displays a compensatory adaptation, but does not completely re-enact normal euthyroid physiology. This invites a study of the clinical consequences of this disparity.
13) Low Thyroid function associated with heart disease risk
HUNT study
14) http://www.ncbi.nlm.nih.gov/pubmed/18443261
Thyrotropin TSH Levels and Risk of Fatal Coronary Heart Disease- The HUNT Study . Norway Arch Intern Med. 2008;168(8):855-860. Bjørn O. Åsvold, MD; Trine Bjøro, MD, PhD; Tom Ivar L. Nilsen, PhD; David Gunnell, MD, PhD; Lars J. Vatten, MD, PhD (Norway) —
70% increased mortality from Heart Disease in higher TSH range (2.5-3.5) In a Norwegian population TSH Levels measured and pts followed over 8 years for death from heart attack 17, 311 women and 8,002 men (without known thyroid or cardiovascular disease or diabetes mellitus at baseline.) Results: In women the hazard ratios for coronary death were 1.41 (95% confidence interval [CI], 1.02-1.96) and 1.69 (95% CI, 1.14-2.52) for women in the intermediate (thyrotropin level, 1.5-2.4 mIU/L) and higher (thyrotropin level, 2.5-3.5 mIU/L) categories, respectively. Conclusions: (TSH) Thyrotropin levels within the reference range were positively and linearly associated with CHD mortality in women. The results indicate that relatively low but clinically normal thyroid function may increase the risk of fatal CHD by 70% .
Antonio C. Bianco M.D.
15) Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine Monotherapy? Sarah J. Peterson Ph.D., Elizabeth A. McAninch M.D., and Antonio C. Bianco M.D. Division of Endocrinology and Metabolism, Rush University Medical Center, 1735 W Harrison St; Cohn Building Rm 212; Chicago, IL 60612, USA
Context: Levothyroxine (LT4) monotherapy is the standard of care for hypothyroidism.
Objective: To determine whether LT4 at doses that normalize the serum TSH is associated with normal markers of thyroid status.
Design: Cross-sectional data from the US National Health and Nutrition Examination Survey (2001–2012) was used to evaluate 52 clinical parameters. LT4-users were compared to healthy controls and controls matched for age, sex, race, and serum TSH. Regression was used to evaluate for correlation with serum thyroxine (T4) and triiodothyronine (T3) levels.
Participants: 9,981 participants with normal serum TSH were identified; 469 were LT4-treated.
Results: Participants using LT4 had higher serum total and free T4 and lower serum total and free T3 than healthy or matched controls. This translated to ∽15–20% lower serum T3:T4 ratios in LT4 treatment, as has been shown in other cohorts. In comparison to matched controls, LT4-treated participants: had higher BMI despite report of consuming less calories/day/kg; were more likely to be taking beta-blockers, statins, and anti-depressants; and reported lower total metabolic equivalents. A serum TSH level below the mean in LT4-treated participants was associated with a higher serum free T4 but similar free and total T3; yet those with lower serum TSH levels exhibited higher serum HDL and lower serum LDL, triglycerides, and CRP. Age was associated with serum free T3:free T4 ratio in all participants; caloric intake was associated in LT4-treated individuals.
Conclusions: In a large population study, participants using LT4 exhibited lower serum T3:T4 ratios and differed in 12/52 objective and subjective measures.
16) Hypothyroidism Symptoms Linger Despite Medication Use, Normal Blood Tests. Study questions value of TSH levels as indicator that disease is under control. Released: 12-Oct-2016 12:05 PM EDT
Source Newsroom: Rush University Medical Center
17) Hypothyroidism symptoms linger despite medication use, normal blood tests October 12, 2016 Rush University Medical Center
New research gives hypothyroidism patients—who often feel dismissed and forgotten—evidence that their persistent symptoms are not just in their heads.
Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
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Monday, April 8, 2013

The TSH Reference Range Wars, Part One,by Jeffrey Dach MD

TSH Wars Part One
TSH Wars
The TSH Reference Range Wars, Part One, 

Click Here for Part Two

by Jeffrey Dach MD

I find it curious that  modern medicine continues to argue within itself on the proper reference range for the TSH test (Thyroid Stimulating Hormone) commonly used to assess thyroid function.  .This TSH test and reference range is the subject of continuous debate and even changing ranges throughout the history of medicine.

Above left image:  TSH Wars with Tank  convoy of Soviet T-72 battle tanks. 
 commons.wikimedia.org/wiki/File:Soviet_T-72_main_battle_tanks.JPEG

The New Reference Range for the TSH - The 2.5 cutoff

Here is a little history of the TSH reference range wars.  In 2002-2003, three professional organizations revised the TSH references range lower from the old 4.5 down to 2.5 or 3.0.  (10)  On the basis of this new range, a larger percentage of the population will be given a diagnosis of a low thyroid condition.

2002 - American Association of Clinical Endocrinologists narrowed the serum TSH reference range to 0.3-3.0 mIU/L, lowering the upper reference end to 3.0.
(Baskin et al. Endocrine Practice 8:457, 2002)

2003- The National Academy of Clinical Biochemistry, Recommends a TSH upper limit of 2.5 mIU/L. (Baloch et al. Thyroid 13:42, 2003 & www nacb.org)

2003 - the consensus panel (Endocrine Society, American Association of Clinical Endocrinologists, and American Thyroid Association) recommended a target TSH range of 1.0 to 1.5 mIU per liter in patients already receiving thyroxine therapy. (12)

In 2007, The endocrine Society issued new guidelines for pregnancy and preconception:

2007 - Endocrine Society Pregnancy Guidelines:
Preconception & 1st trimester - keep TSH below 2.5 mIU/L
2nd and 3rd trimesters - keep TSH below 3.0 mIU/L
(Abalovich et al. JCEM 92: S1-S47, 2007)

After all the above, it was a surprise to see a laboratory that had been using the lower TSH range (0.3 to 2.5) for many years, and then in 2010, switched back to the old range of  0.3 to 5.0. (2)  Many other labs, such as one in Ontario ignores the lower recommendations and continues using the older upper range for TSH of 4.5 (3)
TSH Reference Range Wars Part One Jeffrey Dach MD
TSH Wars Part One
Labs Using Differing Ranges

Another eye opener: When 30 labs were surveyed,  They found that 30% used the manufacturer recommended ranges, 10% used their own and 60 % used an "adapted" range.  Most of the 30 labs used differing reference ranges with the upper range varying from 3.8 to 6.0.  There was no single reference range in use.(10)  In addition, of 9 different manufacturers of TSH test kits used by the labs, they all had differing reference ranges.

Above Image: 40mm guns firing aboard the U.S. aircraft carrier USS Hornet (CV-12) on 16 February 1945, as the planes of Task Force 58 were raiding Tokyo. Note expended shells and ready-service ammunition at right.  16 February 1945. Courtesy Wikimedia commons. 
http://commons.wikimedia.org/wiki/File:40mm_guns_firing_aboard_USS_Hornet.jpg

TSH Reference Ranges Differ For 9 Different Manufacturers Assays (10)


TSH Kit                TSH Range
Roche Elecsys      0.27- 4.0
Immulite 2000     0.40- 4.0
Tosoh A1A           0.34- 3.8
Bayer Centaur      0.35- 5.5
Beckman Access   0.35- 3.5
Abbott AxSym      0.49- 4.7
Abbott Architect   0.35- 4.9
Ortho Eci             0.30- 3.1
TSH Warfare Jeffrey DAch MD
TSH Wars
Mary Shomon Reviews the TSH Wars

An excellent article by Mary Shomon summarizes the debate over what should be accepted as the TSH reference range. (6)  She cites Wartofsky as an advocate for the 2.5 cut off.  Wartofsky and Dickey say (7) :
"We will probably never have an absolutely cutoff value for TSH distinguishing normal from abnormal, but recognition that the mean of normal TSH values is only between 1.18 and 1.4 mU/liter and that more than 95% of the normal population will have a TSH level less than 2.5 mU/liter clearly imply that anyone with a higher value should be carefully assessed for early thyroid failure."
Above left image: Vickers machine-guns 20 September 1944.  http://commons.wikimedia.org/wiki/File:Vickers_machine-guns_fire_in_support_of_troops_crossing_the_Maas-Schelde_Canal.jpg

Carole Spencer MD PHD -
How should the TSH reference range be determined?

Perhaps the most respected expert on the TSH test and reference range is Carole Spencer MD PhD, Professor of Research at the Keck School of Medicine at the University of Southern California. (9-10) Carole Spencer says:
"It is impossible to establish a range using population data.  The TSH upper reference limit is really a moving target. It depends upon the population being studied, the underlying pathology and iodine intake of that population, as well as the specificity of the assay for detecting the various TSH isoforms present in sera."
She also says:
"It is not possible to establish a universal TSH upper limit from population data. An appropriate compromise would be to adopt an empiric TSH reference range approximating 0.3 to 3 mIU/L, as suggested by AACE. It is important to recognize that the upper TSH reference limit is not the therapeutic threshold for initiating levothyroxine replacement therapy. "

Treating Patients with Labs Within Normal Range  ??

The International Hormone Society has written extensively on this issue of Hypothyroidism with Labs in Reference Range, with a Consensus Panel Statement and listing of medical references supporting treatment in these cases (11)

In Addition, the American Academy of Anti-Aging Medicine issued a 2007 "White Paper Guidance" on interpretation of lab tests such as the TSH (12)

They state:
"The use of "natural" thyroid in patients whose TSH levels for example are not yet over 5.5 has stimulated controversial cases where the treating physician has been dragged into court to explain why a thyroid supplement was administered to a patient who is not yet sick? Several, often recent, studies have now been published that show that levels of TSH within the reference range, between 2 and 5.5, in certain categories of patients have been reported to be associated with pathological abnormalities and even diseases. It is therefore to no surprise that the American Association of Clinical Endocrinologists has therefore narrowed in 2002 the serum TSH reference range to 0.3-3.0 mIU/L, lowering the upper reference end to 3. The National Academy of Clinical Biochemistry, the world’s most respectful organisation for editing guidelines on laboratory test interpretation, reduced the upper end of the reference range from 5.5 to 4.1 mIU per liter in 2003. The latter group also stated that “more than 95% of healthy, euthyroid subjects have a serum TSH between 0.4 - 2.5 mIU per liter" and that “patients with a serum TSH above 2.5 mIU per liter, when confirmed by repeat TSH measurement made after three to four weeks, may be in the early stages of thyroid failure, especially if thyroid peroxidase antibodies are detected.” In 2003, the consensus panel (Endocrine Society, American Association of Clinical Endocrinologists, and American Thyroid Association) recommended a target TSH range of 1.0 to 1.5 mIU per liter in patients already receiving thyroxine therapy. " (12)

Questioning TSH for Monitoring Thyroxine Treatment

To make matters worse, studies have shown TSH to be a poor indicator of thyroid status during thyroxine treatment.(13)  A 2005 study from Greece by Alevizaki concluded:
"Patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver. "(13)

They go on to say:
"TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues. The co-administration of T3 may prove more effective in this respect, provided novel suitable preparations are developed. Until this is accomplished, substitution in hypothyroidism should aim at low normal TSH, to ensure normal T3 levels." (13)

Others have questioned the value of T4 monotherapy because some individuals are poor converters and are unable to convert the T4 to T3. (14)

TSH Shifts Up With Age

One problem is that TSH ranges tend to shift up with age. (4)  Older individuals run higher TSH values and this may be "normal" based on gaussian distribution of lab values for the population.

TSH May Be Misleading In Certain Circumstances

In addition, there are clinical situations in which TSH levels may be misleading such as: (5)
1) abnormalities in hypothalamic or pituitary function, including TSH-producing pituitary tumors.
2)  transition periods such as early phase of treatment for hypothyroidism.  Specifically, it takes 6-12 weeks for pituitary TSH secretion to re-equilibrate to the new thyroid hormone status.
3) Following an episode of thyroiditis, including post-partum thyroiditis when discordant TSH and FT4 values may also be encountered.
4) Certain drugs that influence pituitary TSH secretion (i.e. dopamine and glucocorticoids) or thyroid hormone binding to plasma proteins, may also cause discordant TSH values

Articles With Related Content:
The Unreliable TSH Test
TSH WARS Part Two

Jeffrey Dach MD

Links and References
(1) www.ncbi.nlm.nih.gov/pubmed/12625976?dopt=Abstract
Thyroid. 2003 Jan;13(1):3-126.
Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruf J, Smyth PP, Spencer CA, Stockigt JR; Guidelines Committee, National Academy of Clinical Biochemistry. Source Department of Pathology & Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, USA.
------------
changing the reference range back up from 2.5 to 5.0
(2) www.allina.com/ahs/allinalabs.nsf/page/TSHRange10.pdf/$FILE/TSHRange10.pdf
Effective May 4, 2010, there is a new TSH reference range for adults:
Current Reference Range: 0.34 – 2.50 μU/mL
New Reference Range: 0.30 – 5.00 μU/mL
Why was the upper limit for TSH set at 2.5 μU/mL in the first place?
A national guideline published in 2003 recommended lowering the upper limit of TSH to 2.5 μU/mL (NACB in Thyroid. 2003 Jan;13(1):3-126). Based on a population study, this was felt to be the true upper limit for euthyroid individuals after rigorous exclusion of all patients with possible thyroid dysfunction.
Why is the laboratory now raising the upper limit of normal for TSH to 5.0 μU/mL?
More recent studies indicate that an upper limit of 2.5 μU/mL for TSH is too low. Kratzsch et al (Clin Chem. 2005 Aug;51(8):1480-6) showed that after rigorously excluding all patients with possible thyroid dysfunction, a normal range for TSH was 0.12-5.29 μU/mL. Massachusetts General Hospital uses a range of 0.5-4.7 μU/mL (New England Journal of Medicine 2004;351:1548-63) and Mayo Clinic uses a range of 0.3-5.0 μU/mL. Parallel tests of patient specimens at Allina and Mayo Clinic show the same TSH results and a recent reference range validation performed at AML indicates that the normal range for our population is consistent with the one used at Mayo Clinic.
(3) www.oaml.com/PDF/FINALTSH%20Guideline%20July%2018,%2007.pdf
Ontario Clinical Lab July 2007 Guidelines
5. TSH Reference Intervals In the literature, discussion is ongoing as to the appropriate TSH reference range; some laboratories report a lower value for the upper limit of normal (between 2.5‐3.0 mU/L). Ontario community laboratories have elected to continue to report the higher upper limit of normal (4.5 to 5.5 mU/L). The OAML Quality Assurance Committee and its Expert Panel on thyroid disease will update the reference range when there is evidence‐based literature supporting such a change.
Lowering the TSH Range to 2.5
TSH shifts up with age
(4) jcem.endojournals.org/content/92/12/4575.long
Age-Specific Distribution of Serum Thyrotropin and Antithyroid Antibodies in the U.S. Population: Implications for the Prevalence of Subclinical Hypothyroidism
Martin I. Surks and    Joseph G. Hollowell  The Journal of Clinical Endocrinology & Metabolism December 1, 2007 vol. 92 no. 12 4575-4582
Recently a discussion has begun concerning lowering the upper limit of the TSH reference range to 2.5 mIU/liter
Results: Without thyroid disease, 10.6% of 20- to 29-yr-olds had TSH greater than 2.5 mIU/liter, increasing to 40% in the 80+ group, 14.5% of whom had TSH greater than 4.5 mIU/liter. When TSH was greater than 4.5 mIU/liter, the percentage with antibodies was 67.4% (age 40–49 yr) and progressively decreased to 40.5% in the 80+ group. TSH frequency distribution curves of the 80+ group with or without antibodies was displaced to higher TSH, including TSH at peak frequency. The 97.5 centiles for the 20–29 and 80+ groups were 3.56 and 7.49 mIU/liter, respectively. Seventy percent of older patients with TSH greater than 4.5 mIU/liter were within their age-specific reference range.
Conclusion: TSH distribution progressively shifts toward higher concentrations with age. The prevalence of SCH may be significantly overestimated unless an age-specific range for TSH is used.
-----------------------
(5)
www.aacc.org/sitecollectiondocuments/nacb/lmpg/thyroid/thyroid-fullversion.pdf
LABORATORY MEDICINE PRACTICE GUIDELINES.
Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease.
It is important to recognize the clinical situations where serum TSH or FT4 levels may be diagnostically misleading (see Table 1).
These include abnormalities in hypothalamic or pituitary function, including TSH-producing pituitary tumors (27-29).
Also, as shown in Figure 2, serum TSH values are diagnostically misleading during transition periods of unstable thyroid status, such as occurs in the early phase of treating hyper- or hypothyroidism or changing the dose of L-T4.
Specifically, it takes 6-12 weeks for pituitary TSH secretion to re-equilibrate to the new thyroid hormone status (30). These periods of unstable thyroid status may also occur following an episode of thyroiditis, including post-partum thyroiditis when discordant TSH and FT4 values may also be encountered. Drugs that influence pituitary TSH secretion (i.e. dopamine and glucocorticoids) or thyroid hormone binding to plasma proteins, may also cause discordant TSH values [Section-3 B3(c)vi].
----------------------------------------------------------------
(6) thyroid.about.com/od/gettestedanddiagnosed/a/tshtestwars.htm
The TSH Reference Range Wars: What's "Normal?", Who is Wrong, Who is Right... And What Does It All Mean For You and Your Health? By Mary Shomon,
About.com Guide Updated June 19, 2006 3.
If your TSH test levels come in below 0.5, or above 2.5-3.0, and your doctor is saying these levels are normal, make him or her aware of the AACE and American Association for Clinical Chemistry Laboratory Medicine Practice Guidelines and their 0.3 to 3.0 new reference range. Ask the doctor if he or she will consider a different diagnosis and treatment based on this new information.
----------------------------
(7) jcem.endojournals.org/content/90/9/5483.long
jcem.endojournals.org/content/90/9/5483/F1.expansion.html
The Evidence for a Narrower Thyrotropin Reference Range Is Compelling
The Evidence for a Narrower Thyrotropin Reference Range Is Compelling Leonard Wartofsky and Richard A Dickey Endocrinology & Metabolism September 1, 2005 vol. 90 no. 9 5483-5488 Drs.
Wartofsky and Dickey defend the shift to the new range, with some caveats. They say:
"We will probably never have an absolutely cutoff value for TSH distinguishing normal from abnormal, but recognition that the mean of normal TSH values is only between 1.18 and 1.4 mU/liter and that more than 95% of the normal population will have a TSH level less than 2.5 mU/liter clearly imply that anyone with a higher value should be carefully assessed for early thyroid failure."
-------------------------------------
(8) fpn.imng.com/fileadmin/content_pdf/fpn/archive_pdf/vol37iss20/71244_main.pdf
Upper Limit of TSH Reference Range Debated. BY SHERRY BOSCHERT. San Francisco Bureau. Providers looking for a defined upper limit of the statistically Family Practice News
----------------------------------
Carole Spencer MD PHD
(9) www.endocrinetoday.com/view.aspx?rid=28719
on June 10, 2008
How should the TSH reference range be determined?
It is impossible to establish a range using population data.  The TSH upper reference limit is really a moving target. It depends upon the population being studied, the underlying pathology and iodine intake of that population, as well as the specificity of the assay for detecting the various TSH isoforms present in sera. Its essential to ensure that individuals with any degree of thyroid dysfunction are excluded from reference range calculations. However, there are some individuals that are TPOAb-negative and yet have thyroid dysfunction. The inclusion of such individuals has the potential to skew the TSH reference limits to some extent. Carole Spencer, MD, PhD Carole Spencer Surks and Hollowell reported that the TSH reference range increased with age and concluded that perhaps a higher TSH is a natural consequence of aging. We interpret this finding differently. It is well known that in the United States the prevalence of autoimmune thyroid disease increases with age and not all affected individuals display TPOAb. In the SHIP study, there was a trend for a decrease in TSH with age, despite excluding individuals with nodules visible on ultrasound. Both the NHANES and SHIP studies did their best to screen out occult thyroid dysfunction yet opposite trends in TSH were seen with aging. These trends are less likely to be the physiological effect of aging, but more likely the influence of occult thyroid pathology specific to that population contaminating the data and causing these age-related shifts in TSH. It is not possible to establish a universal TSH upper limit from population data. An appropriate compromise would be to adopt an empiric TSH reference range approximating 0.3 to 3 mIU/L, as suggested by AACE. It is important to recognize that the upper TSH reference limit is not the therapeutic threshold for initiating levothyroxine replacement therapy. Instead, the clinical response to a confirmed mildly elevated TSH should be determined on an individual basis. Carole Spencer, MD, PhD, is a Professor of Research at the Keck School of Medicine at the University of Southern California.
(10)
www.aacc.org/events/expert_access/2009/July/Documents/AACC_Spencer_NoAnimOrNotes.pdf www.aacc.org/events/expert_access/2009/july/pages/default.aspx
Contemporary Issues in Thyroid Disease Measurements excellent review of varying TSH upper ranges for various labs, and societies based on iodine intake, ethnicity and age.
Dr. Carole Spencer received a 1st. Class Bachelor of Science degree in Applied Biochemistry from Bath University of Technology in England, U.K., and later a PhD from the Department of Medicine at Glasgow University, Scotland, U.K. In 1977, she immigrated to the United States and joined the University of Southern California in Los Angeles.
Dr. Spencer holds the rank of Professor of Medicine in the Department of Medicine at USC, where she is a licensed Medical Technologist, and directs the USC Endocrine Laboratories. Her research career has focused on the clinical and laboratory aspects of thyroid disease and treatment, and she has authored or co-authored more than 80 original papers, chapters and monographs on the clinical and laboratory aspects of thyroidology.
Dr. Spencer is a past President of the American Thyroid Association and a member of the ATA Laboratory Services Committee. She is the recipient of numerous outstanding speaker awards from the American Association for Clinical Chemistry, and she received the 2004 Distinguished Scientist Award from the National Academy of Clinical Biochemistry.
---------------------------------
(11)
www.intlhormonesociety.org/ref_cons/Ref_cons_9_thryoid_treatment_of_clinically_hypothyroid_biochemically_hypothyroid_patients.pdf
International Hormone Society Hypothyroidism with Labs in Reference Range References Supporting Treatment
-----------------------------------------------
(12) www.worldhealth.net/pdf/WhitePaper_GuidancePhysicians-HRT.pdf
White Paper Guidance for Physicians on Hormone Replacement Therapy (HRT)
Released 27 April 2007; Updated 22 May 2007
The use of "natural" thyroid in patients whose TSH levels for example are not yet over 5.5 has stimulated controversial cases where the treating physician has been dragged into court to explain why a thyroid supplement was administered to a patient who is not yet sick? Several, often recent, studies have now been published that show that levels of TSH within the reference range, between 2 and 5.5, in certain categories of patients have been reported to be associated with pathological abnormalities and even diseases. It is therefore to no surprise that the American Association of Clinical Endocrinologists has therefore narrowed in 2002 the serum TSH reference range to 0.3-3.0 mIU/L, lowering the upper reference end to 3. The National Academy of Clinical Biochemistry, the world’s most respectful organisation for editing guidelines on laboratory test interpretation, reduced the upper end of the reference range from 5.5 to 4.1 mIU per liter in 2003. The latter group also stated that “more than 95% of healthy, euthyroid subjects have a serum TSH between 0.4 - 2.5 mIU per liter" and that “patients with a serum TSH above 2.5 mIU per liter, when confirmed by repeat TSH measurement made after three to four weeks, may be in the early stages of thyroid failure, especially if thyroid peroxidase antibodies are detected.” In 2003, the consensus panel (Endocrine Society, American Association of Clinical Endocrinologists, and American Thyroid Association) recommended a target TSH range of 1.0 to 1.5 mIU per liter in patients already receiving thyroxine therapy.
Questioning Use of TSH as marker for Thyroid Hormone Therapy
(13) http://www.ncbi.nlm.nih.gov/pubmed/16416346
Wien Klin Wochenschr. 2005 Sep;117(18):636-40.
TSH may not be a good marker for adequate thyroid hormone replacement therapy.
Alevizaki M, Mantzou E, Cimponeriu AT, Alevizaki CC, Koutras DA.
Source Endocrine Unit, Dept Medical Therapeutics, Alexandra Hospital, Athens University School of Medicine, Athens, Greece.
The objective of this study was to evaluate parameters of thyroid function and indices of peripheral thyroid hormone action (such as SHBG) in patients whose hypothyroidism was considered well controlled under current criteria.
Eighty-five patients with T4-treated hypothyroidism, 28 of whom had athyria, were compared with 114 normal individuals with the same TSH levels. T3 levels were significantly lower in hypothyroidism although mean T4 and fT4 levels were significantly higher. Furthermore, mean SHBG levels were significantly lower in hypothyroidism independently of age. The difference remained when stricter criteria for adequate treatment were applied (TSH < 2.5 microgU/ml). Significant negative correlations were found between logTSH and T3. The slopes of the regression lines of T3 to TSH were significantly different in the control group and the hypothyroid group:
thus, for the same TSH levels, T3 levels were lower in the hypothyroid group.
We conclude that patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver.
TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues. The co-administration of T3 may prove more effective in this respect, provided novel suitable preparations are developed. Until this is accomplished, substitution in hypothyroidism should aim at low normal TSH, to ensure normal T3 levels.
Questioning Levothyroxine Monotherapy
(14) www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022552
Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients Damiano Gullo#*, Adele Latina#, Francesco Frasca, Rosario Le Moli, Gabriella Pellegriti, Riccardo Vigneri Endocrine Unit, Department of Clinical and Molecular Biomedicine, University of Catania Medical School, Garibaldi-Nesima Hospital, Catania, Italy
(15)
mospace.umsystem.edu/xmlui/bitstream/handle/10355/3843/WhichLabTestsHypothyroidism.pdf?sequence=1
Which lab tests are best when you suspect hypothyroidism?
www.jfponline.com  VOL 57, NO 9 / SEPTEMBER 2008 Glenn D. Miller, MD, and Jared C. Rogers, MD University of Illinois College of Medicine and Methodist Medical Center of Illinois, Peoria Sandra L. DeGroote, MLIS University of Illinois College of Medicine Library of the Health Sciences, Peoria ---
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The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician -- patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.
Link to this article:http://jeffreydachmd.com/2013/03/tsh-wars-part-one/
http://jeffreydach.com/2011/08/30/the-tsh-reference-range-wars-by-jeffrey-dach-md.aspx
Copyright (c) 2013 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.
FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a 'fair use' of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.