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Hypothyroidism: Sensitive Diagnosis and Optimal Treatment of All Types and Grades - A Comprehensive Hypothesis

Based on a Review of the Standard and “Alternative” Literature and Extensive Clinical Experience
John V. Dommisse, MD, MBChB, FRCP(C)*

Abstract. The hypothesis of this paper is that hypothyroidism (in its various forms and degrees) is often undiagnosed in its grade 3 primary, secondary (pituitary), tertiary (hypothalamic), and non-thyroidal illness hypothyroidism versions; and under-treated in all versions, including its grades 1 and 2 primary hypothyroidism versions. The current standard and alternative approaches to the diagnosis and management of hypothyroidism, and their logical inconsistencies and inadequacies, are discussed. The biggest losers in this neglectful situation are elderly, memory-loss, mood-disordered, chronically fatigued, or overweight patients.

An extensive review is presented, which is then coupled with logical argument and clinical experience to clarify the hypothesis. Methods employing the free thyroid hormone levels (FT4 and FT3 ), by the accurate direct and tracer-dialysis methods, respectively, and a lower normal range for the thyroid stimulating hormone level are described.

These help optimise the newly-developed diagnostic strategies. Their superiority over the standard conventional and alternative approaches are suggested by inferential argument and by the author’s personal experience of his own case of post-surgical (thyroglossal cystectomy) hypothyroidism - missed by the medical profession for 36 years - and his clinical experience with approximately 5,000 patients over a 19-year time period.

Diagnostic strategies and treatment methods are described which refute traditional objections to measuring the FT3 serum level - at least in the case of the serum test done by the dialysis method - and to treating with varying combinations of both T4 and either T3 or T4 /T3 combination hormone preparations. The objections about aggressive thyroid treatment causing or aggravating osteoporosis and cardiac arrhythmias are found (in the author’s practice) to not only be overblown, but to be entirely non-existent when corrections are made for certain mineral, vitamin, amino acid, and sex-and growth-hormonal deficiencies.

To see the whole paper go to:



Thyroid Replacement in Clinically Hypothyroid Patients who have Free Thyroxine or Thyroid Stimulating Hormone within 95% Reference Intervals; 23.07.07.

Dr Skinner?

There is controversy in the medical profession on the advisability of thyroid replacement in patients whose thyroid chemistry in particular the free thyroxine (FT4) and or thyroid stimulating hormone (TSH) lie inside the laboratory 95% reference intervals. This is a central issue in an ongoing GMC v Skinner Fitness to Practice Hearing.

I thought it would be relevant to establish in part measure what proportion of colleagues practising endocrinology had ever provided thyroid replacement in these situations (Tables 1, 2 and 3).

A total of 173 respondents replied within 28 days of receiving the questionnaire wherein 56 of the respondents requested anonymity. There were 93% respondents who had at least once provided thyroid replacement to patients with TSH level above the 95% reference intervals with a lesser proportion of 69% for patients with FT4 level below the lower limit of the 95% reference interval and a lower but significant proportion (12%) where both were inside the 95% reference intervals. There was little difference in results between eponymous and anonymous respondents.

These conclusions do not engross information on the precise levels of thyroid hormone within a given reference interval. This matter is often cheerfully ignored by certain colleagues who advance the strange concept that if (for example) a TSH value is within a reference interval then the patient is not hypothyroid irrespective of the level of the hormone within that interval. La Place and his contemporary Gauss – they of probability distribution fame – would be astonished to learn that Gaussian theory is now being applied to the distribution of thyroid hormone levels and then, erroneously, to the frequency of hypothyroidism.

They would also be astonished to learn that there is no evidence correlating thyroid hormone values within the 95% reference intervals with the frequency and/or severity of hypothyroidism and that an unproven statistic has been transmuted into a gold standard of diagnosis wherein hypothyroidism cannot apparently exist if thyroid chemistry lies within 95% reference intervals. In the absence of secure correlative evidence, only one situation permits this approach, namely if a condition has been defined ab initio via laboratory findings which, for example, might apply to hypercholesterolaemia or even sub clinical hypothyroidism where the condition has been defined as having a raised TSH level above the 95% reference interval. The ‘coincidence’ of a 5% incidence of hypothyroidism – and indeed of other 5% disease frequencies similarly derived - requires critical re-examination.

It must be emphasised that the frequency responses recorded in Tables 1, 2 and 3 do not represent usual or current practice of the respondents; there are of course many interpretations from information presented outwith a contextual framework.

There is an urgent case to examine the efficacy of thyroid replacement in patients who have clinical evidence of hypothyroidism with clinical chemistry lying within 95% intervals.

I thank colleagues for their courteous and timely responses to this questionnaire.


Sunscreen May Cause Hypothyroidism

The UV filter benzophenone 2 inactivates human recombinant thyroperoxidase in vitro and disturbs thyroid hormone homeostasis in rats

C Schmutzler1, A Bacinski1, P Ambrugger2, H Klammer3, W Wuttke3, A Grüters2, H Jarry3 & J Köhrle1

1Institut für Experimentelle Endokrinologie, Charité - Universitätsmedizin Berlin, Berlin, Germany; 2Institut für Experimentelle Pädiatrische Endokrinologie, Charité - Universitätsmedizin Berlin, Berlin, Germany; 3Experimentelle und klinische Endokrinologie, Universitäts-Frauenklinik Göttingen, Göttingen, Germany.

UV filters are produced in high amounts for multiple uses. Their main application is in sun lotions for skin protection against accelerated ageing or cancer, but they are also found in many other cosmetics or in plastic materials to prevent their radiation-induced damage. Regardless of these protective properties, UV filters seem to interfere with both the reproductive and the thyroid endocrine axis. We here screened for effects of the UV filter benzophenone 2 (BP2) on thyroid hormone biosynthesis and serum levels. Possible inhibition of iodide uptake was examined using the sodium iodide symporter-expressing rat thyroid cell line FRTL-5, but inhibition was not observed. Effects on human thyroperoxidase (TPO) were measured using extracts prepared from human FTC-238 cells stably transfected with human TPO. BP2 inhibited TPO activity with IC50 values of 0.45 and 0.37 μmol H2O2 reduced per min and per mg protein in the guaiacol and the iodide oxidation assay, respectively. The values for the well known TPO inhibitor, genistein, were 61.1 and 2.06 μmol H2O2 × min−1 × mg−1, respectively. BP2 in combination with H2O2 inactivated TPO, an effect that was prevented by adequate iodide concentrations in the reaction mixture. To examine in vivo effects of BP2, adult female ovariectomized rats were treated via gavage for 5 days with olive oil (control) or with 10, 33, 100, 333 and 1000 mg/kg body weight BP2 (12 animals per group). Serum total T4 was reduced and TSH was increased; differences were significant for 333 and 1000 mg/kg BP2. The observed decrease in serum total T3 was not significant. Our data indicate that BP2 interferes with thyroid hormone biosynthesis, thereby disturbing thyroid hormone homeostasis. This may have consequences for human health, especially in the context of a still prevailing iodide deficiency in many parts of the world. Supported by EU grants.

Endocrine Abstracts (2006) 11 P429


Thyroid Hormone replacement therapy in primary hypothyroidism: a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone.

Escobar-Morreale HF, Botella-CarreteroJI, Gomez-Bueno M, Galan JM, Barrios V, Sancho J – Archives of Intern Med 2005 Mar 15;142(6)155

This study looked at 28 women with overt hypothyroidism.  They were given 100mcg thyroxine for 8 weeks, then 75mcg thyroxine and 5mcg liothyronine for 8 weeks.  All patients were then given 87.5mcg thyroxine and 7.5 mcg liothyronine.  The doctors noted that the last combination resulted in over-replacement.   The results were that 12 patients preferred combination treatment, 6 patients preferred the add-on combination treatment, 2 patients preferred standard treatment an d 6 patients had no preference.

Amazingly, the conclusions were that “Physiologic combinations of L-thyroxine plus liothyronine do not offer any objective advantage over l-thyroxine along, yet patients prefer combination treatment.”

I think the important word here is “objective”.  Research is not accepted as good unless results can be seen in blood tests, never mind how the patient feels!


The Birmingham Elderly Thyroid Study (BETS): TSH and fT4 values in 5784 community-living subjects aged 60 and over

JV Parle1, JA Franklyn2, S Wilson1, L Roberts1, R Holder1, MC Sheppard2, FDR Hobbs1, A Roalfe1, M Gammage2, C Heath1 & H Pattison

The researchers investigated associations between thyroid function, presence of atrial fibrillation and cognitive function in a large general practice-based study conducted from December 2002-November 2004. Subjects with a previous history of thyroid disease or currently taking thyroxine or anti-thyroid drugs were excluded.

There were 5784 subjects aged 65 or over with the average age of subjects being  73.5 years; 49.3% male (mean age 73.3), 50.7% female (average age 73.7). Reference ranges for TSH were 0.4-5.5mU/l and fT4 9-20 pmol/l

Overall, 2.6% of subjects had low serum TSH  and 3.3% had high serum TSH values.  The average serum fT4 was 9.5 pmol/l.   There were 53 subjects with a serum TSH 10 or higher and of these 23 had fT4 values below the reference range. The average serum fT4 was 13.0 pmol/l Among those with low but detectable TSH

The researchers concluded that a high proportion of subjects over 60 have both hypothyroidism and hyperthyroidism, especially subclinical disease.


Relations of Thyroid Function to Body Weight: Cross-sectional and Longitudinal Observations in a Community-Based Sample

Abstract summarised from:
Arch Intern Med. 2008; 168(6): 587-592
Caroline S. Fox, MD, MPH; Michael J. Pencina, PhD; Ralph B. D’Agostino, PhD; Joanne M. Murabito, MD; Ellen W. Seely, MD; Elizabeth N. Pearce, MD; Ramachandran S. Vasan, MD

Background: Overt hypothyroidism and hyperthyroidism may be associated with weight gain and loss. We assessed whether variations in thyroid function within the reference (physiologic) range are associated with body weight.

Methods:  Patients taking part in the Framingham Offspring Study who attended 2 consecutive routine examinations, were not receiving thyroid hormone therapy, and had TSH levels of 0.5 to 5.0 and follow-up levels of 0.5 to 10.0 were included in this study. TSH concentrations were related to body weight and body weight change during 3.5 years of follow-up.

Results:  Weight increased progressively from 64.5 to 70.2 kg in the people who were in the lowest to highest quarters of the TSH range in women and from 82.8 (lowest quarter) to 85.6 kg (highest quartier) in men. During 3.5 years of follow-up the average body weight increased by 1.5 (5.6) kg in women and 1.0 (5.0) kg in men. Baseline TSH levels were not associated with weight change during follow-up. However, an increase in TSH concentration at follow-up was positively associated with weight gain in women (0.5-2.3 kg across increasing quarters of TSH levels) and men (0.4-1.3 kg across quarters of TSH levels).

Conclusions:  Thyroid function (as assessed by serum TSH concentration) within the reference range is associated with body weight in both sexes. Our findings raise the possibility that modest increases in serum TSH concentrations within the reference range may be associated with weight gain.