TSH Wars, Part Two by Jeffrey Dach MD

Simulation of endocrinologists defending Synthroid and the TSH test. Courtesy of wikimedia commons. Actually Australian soldiers manning a Vickers machine gun at Sanananda in January 1943; Australian War Memorial

Simulation of endocrinologists defending Synthroid and the TSH test.

TSH Wars Part Two by Jeffrey Dach MD

This article is part two, For part one Click Here.  For part three.

The Low Thyroid Condition – Case Report

Mary 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 Zuloft.   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.

Upper left Image: Simulation of  endocrinologists defending Synthroid and the TSH test. Courtesy of wikimedia commons. Actually Australian soldiers manning a Vickers machine gun at Sanananda in January 1943; Australian War Memorial

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.(1)

Switching from Levothyroxine to Natural Thyroid

Mary was switched from Levothyroxine to Naturethroid 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.

TSH Wars

TSH Wars

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).

Left image: USS Hornet WW2 guns firing,  courtesy of wikimedia commons.

In 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.

Upper Left Image: Endocrinologists defending the TSH Test and Synthroid courtesy of Wikimedia Commons.

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)

Japan 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?

The 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.

Update Oct 2016: Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine Monotherapy?

Dr Antionio Bianco endocrinologist and past president of the ATA from Rush Medical School in Chicago writes article in Oct 2016 Journal of Clinical Endocrinology and Metabolism:  Is a Normal TSH Synonymous with “Euthyroidism” in Levothyroxine Monotherapy? (15)

Dr Antonio Bianco studied 469 patients treated with levothyroxine (T4 only) for hypothyroidism, and compared to normal controls.  He found: 1) Levothyroxine treated patients ” had higher serum free T4 and lower serum free T3 than healthy or matched controls.”  Dr Bianco found that Levothyroxine treated patients “were more likely to be overweight despite consuming less calories, and more likely to be taking anti-depressants, and anti-cholesterol (statin) drugs compared to matched controls.”   Clearly, Dr Antonio Bianco has reported that TSH in the normal range for many levothyroxine treated patients does NOT provide adequate symptom relief.

Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Florida 33314
954-792-4663
http://www.jeffreydach.com/
http://www.drdach.com/
http://www.naturalmedicine101.com/
http://www.truemedmd.com/
http://www.bioidenticalhormones101.com/

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.jeffreydach.com
www.drdach.com
www.naturalmedicine101.com
www.bioidenticalhormones101.com
www.truemedmd.com

Links and References

1) Delange, François, Bruno de Benoist, and Hans Bürgi. “Determining median urinary iodine concentration that indicates adequate iodine intake at population level.” Bulletin of the World Health Organization 80.8 (2002): 633-636.
Determining median urinary iodine concentration that indicates adequate iodine intake at population level

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
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Summary
Article Name
TSH Wars Part Two
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TSH Wars Part Two
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Jeffrey Dach MD