Tag Archives: Conditions and Diseases

Underactive thyroid disease – a modern approach

9 Jun

The Problem

A patient comes to the doctor concerned about longstanding fatigue symptoms. She knows of a family history of underactive thyroid disease and is worried her thyroid is not working properly

Introduction and some basic concepts

[from Basic endocrinology : for students of pharmacy and allied health sciences, edited by Constanti et al (1998; ISBN 9780203301739) ]

The thyroid gland lies in front of the trachea below the larynx. The hypothalamus and pituitary control normal secretion of thyroid hormones. The thyroid hormones in turn control the body’s metabolism. The two active hormones are iodinated derivatives of the amino acid tyrosine. Nearly 90% of the output is thyroxine (T4) containing four iodine atoms while nearly 10% of the output is triiodothyronine (T3) containing three iodine atoms. In health < 1% “reverse” T3 (rT3) is released; this increases in presence of severe illness or starvation. In the bloodstream the thyroid hormones are extensively bound to plasma proteins, principally thyroxine binding globulin (TBG).

Note that in patients on T4 replacement all T3 is produced by peripheral conversion, and so circulating T4 levels may need to be maintained slightly above the “normal” reference range to generate adequate tissue T3 concentrations.

So far so good that is what medical students and other healthcare professionals have been taught to decades. The thyroid stimulating hormone from the pituitary goes up when/if thyroid hormone levels too low, and vice versa.

However this is not the whole story. A more detailed appreciation of the nuances of thyroid hormone metabolism are required to appreciate why so many people with underactive thyroid disease continue to struggle to regain normal health. For example, the story of Coralie Phillips and Donna Roach gives pause for thought about one of the most neglected conditions in general medicine http://www.thyroidbooks.co.uk/ .

Underactive thyroid disease (UAT) is considered simple to diagnose and simple to treat. Luckily this is the case most of the time. Unfortunately when the approach does not seem to be working effectively patients are labelled as difficult or dismissed as mentally ill instead. The medical establishment generally has failed to treat people with UAT scientifically by looking at factors which may conspire to prevent the neat outcome which is expected.

The purpose of this brief essay is to highlight these pitfalls in the hope that fewer people with UAT will suffer in future.

Modern thyroid hormone biochemistry

Role of vitamin D

It seems that adequate levels of vitamin D are necessary to maintain thyroid health.

For example (http://www.endocrine-abstracts.org/ea/0032/ea0032p1008.htm): In this study of 100 patients with autoimmune hypothyroidism compared to 100 subjects as control group, the higher vitamin D deficiency rates besides lower vitamin D levels in the Hashimoto group together with the inverse correlation between vitamin D and anti-TPO suggest that vitamin D deficiency may have a role in the autoimmune process in Hashimoto’s thyroiditis.

Conversely, some evidence emerging that high levels of T3 may suppress vitamin D levels (e.g. http://endo.endojournals.org/content/154/2/609.short) This may be one mechanism for bone losing state of untreated hyperthyroidism (or over-treatment of UAT)

Role of vitamin B12

A new abstract summarises the impact of low vitamin B12 on thyroid disease (and other [geriatric] conditions http://www.bioline.org.br/abstract?rc13008):

Vitamin B12 deficiency is a common condition in the elderly. It is repeatedly overlooked due to multiple clinical manifestations that can affect the blood, neurological, gastrointestinal, and cardiovascular systems, skin and mucous membranes. The various presentations of vitamin B12 deficiency are related to the development of geriatric syndromes like frailty, falls, cognitive impairment, and geriatric nutritional syndromes like protein-energy malnutrition and failure to thrive, in addition to enhancing aging anorexia and cachexia. Therefore, interventions must be developed to include their screening and diagnosis to make early and appropriate treatment to prevent its complications before they become irreversible.

Role of trace minerals

A detailed overview of heavy metals by a nanotechnology team illustrates how important optimising the levels can be for cellular health and ascorbic acid/Krebs cycle [http://www.ijsrp.org/research-paper-0413/ijsrp-p16110.pdf]

Iron (Fe) Contained in hemoglobin and myoglobin which are required for oxygen transport in the body. Part of the cytochrome p450 family of enzymes. Anemia is the primary consequence of iron deficiency. Excess iron levels can enlarge the liver, may provoke diabetes and cardiac falurer. The genetic disease hemochromatosis results from excess iron absorption. Similar symptoms can be produced through excessive transfusions required for the treatment of other diseases.

Copper (Cu) Contained in enzymes of the ferroxidase (ceruloplasmin?) system which regulates iron transport and facilitates release from storage. A structural element in the enzymes tyrosinase, cytochrome c oxidase, ascorbic acid oxidase, amine oxidases, and the antioxidant enzyme copper zinc superoxide dismutase. A copper deficiency can result in anemia from reduced ferroxidase function. Excess copper levels cause liver malfunction and are associated with genetic disorder Wilson’s Disease

Manganese (Mn) Major component of the mitochondrial antioxidant enzyme manganese superoxide dismutase. A manganese deficiency can lead to improper bone formation and reproductive disorders. An excess of manganese can lead to poor iron absorption.

Iodine (I) Required for production of thyroxine which plays an important role in metabolic rate. Deficient or excessive iodine intake can cause goiter (an enlarged thyroid gland).

Zinc (Zn) Important for reproductive function due to its use in FSH (follicle stimulating hormone) and LH (leutinizing hormone). Required for DNA binding of zinc finger proteins which regulate a variety of activities. A component of the enzymes alcohol dehydrogenase, lactic dehydrogenase carbonic anhydrase, ribonuclease, DNA Polymerase and the antioxidant copper zinc superoxide dismutase. An excess of zinc may cause anemia or reduced bone formation.

Selenium (Se) Contained in the antioxidant enzyme glutathione peroxidase and heme oxidase. Deficiency results in oxidative membrane damage with different effects in different species. Human deficiency causes cardiomyopathy (heart damage) and is known as Keshan’s disease.

Fluorine (Fl) Constituent of bones and teeth. Important for tooth development and prevention of dental caries. Derives from water, tea, and fish.

Cobolt (Co) Contained in vitamin B12. An excess may cause cardiac failure.

Molybdenum (Mo) Contained in the enzyme xanthine oxidase. Required for the excretion of nitrogen in uric acid in birds. An excess can cause diarrhea and growth reduction.

Chromium (Cr) A cofactor in the regulation of sugar levels. Chromium deficiency may cause hyperglycemia (elevated blood sugar) and glucosuria (glucose in the urine).

A recent Turkish paper indicates low zinc levels in saliva (and so plasma) in people with UAT [http://www.turkjem.org/sayilar/79/buyuk/1-4.pdf]. It is not known if this is a cause or effect of UAT but suggests that people with UAT should ensure zinc levels are optimised.

Role of reverse T3?

A recent study highlights the dangers of subclinical hyperthyroidism considering healthy aging associated with decline in T3, unchanged levels of T4, with rise in TSH and rT3 [http://goo.gl/WCUk8]

The process of normal aging affects the hypothalamic-pituitary-thyroid axis in a number of ways, resetting of the set point being the most important of them. Contrary to the earlier belief, longevity has been reported to be associated with high serum TSH. Most recent studies have demonstrated an age dependent decline in serum free T3 levels, whereas FT4 levels remains relatively unchanged and TSH & rT3 levels increase with age. Two recent meta-analyses have shown increased risk of adverse cardiovascular outcomes in patients younger than 65 years of age, but not in those more than 65 year old. There is a good number of evidence documenting increased mortality in elderly individual with sub- clinical hyperthyroidism, which should be kept in mind while treating mildly elevated TSH in these patients. It is also important to remember that thyroid functions in the elderly closely mimics that found in sick euthyroid syndrome.

People with UAT recognise that rT3 levels can rise while they are ill. They make a good argument that rT3 levels ought to be checked in cases of poor response to standard treatment. If rT3 is raised then clearly the the patient is ill and efforts need to be made to restore her/him to biochemical euthyroid state.

Thyroid stimulating hormone response is not predictable

A recent paper by JEM Midgley highlights the problem with depending on TSH to determine whether or not a person with thyroid disease is adequately treated [http://jcp.bmj.com/content/66/4/335.abstract and http://www.hindawi.com/journals/jtr/2012/438037/]

Our data suggest that the states of hypothyroidism, euthyroidism and hyperthyroidism can be regarded as differently regulated entities. The apparent complexity could be replicated by mathematical modelling suggesting a hierarchical type of feedback regulation involving patterns of operative mechanisms unique to each condition. For clinical purposes and assay evaluation, neither the standard model relating logTSH with FT4, nor an alternative model based on non-competitive inhibition can be reliably represented by a single correlation comparing all samples for both hormones in one all-inclusive group.

Conclusion and approach to the patient

UAT is a common condition though there is still a lot to learn how to accurately diagnose it in all patients. Even if the diagnosis is not elusive the patient’s response to treatment is occasionally not what is expected.

To ensure improved diagnostic accuracy free T3 ought to be checked for all patient suspected of suffering UAT.

Thus it is my practice to check the following in a person who presents with a longstanding history of fatigue with no obvious abnormality on physical examination:

  • Full blood count with vitamin B12, folic acid and transferrin saturation index for iron status
  • Thyroid function test, including free T3 as well as free T4 and TSH
  • C-reactive protein
  • Vitamin D level and calcium profile

If patient is proved to have UAT, treatment is started at 25 mcg daily of thyroxine. The patient will be reviewed approximately 2 months later when thyroid function is rechecked with fT3, as well as checking thyroid peroxidase autoantibody (for autoimmune thyroid disease). If there has been a poor response to treatment, copper, zinc and 9am cortisol level should also be checked. rT3 should be checked in all poor responders to treatment too; this is recommended by Thyroid UK.

For details about signs and symptoms of UAT see for example: patient.co.uk

Some patient resources


Thyroid UK – http://thyroiduk.healthunlocked.com/ http://www.thyroiduk.org.uk/tuk/index.html


American Thyroid Association – http://www.thyroid.org/

Association Française des Malades de la Thyroïde – http://www.asso-malades-thyroide.org/

Petition – Better Endocrinological Service and Treatment for Thyroid Patients in United Kingdom

If you agree that more should be done for people with thyroid disease, then please sign the petition here

David Lewis
June 2013

Nothing to see here – General Practice serves our children well

20 Feb

February 19, 2013 UK readers awoke to the headline that NHS is failing the children. Why?

  • Kids with meningococcal disease are turned away rather than sent to hospital to be cured;
  • Children with asthma are not given adequate treatment;
  • Too many children are admitted to paediatric wards with minor illnesses
  • Doctors prescribe too many drugs which have not been tested on children
  • General practitioners do not have proper postgraduate training in child health

At face value such accusations are depressing. The accusations sully the credibility of GPs who are constantly berated for some failing or other every week in the Britain.

Here I hope to show that the accusations are baseless. General practitioners are fantastic physicians who can manage any patient in first contact doctor setting from cradle to grave.

Meningococcal disease in children

This myth perpetuated in the article that children are turned away is based on an article published in 2006 [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)67932-4/abstract, accessed Feb 20, 2013]

Much has changed since that article was published. In any event the study makes no mention of the fate of the fatalities many of whom, one may argue, would have died anyway. Be that as it may, meningococcal disease is less common now Haemophilus influenzae type B (HiB) immunisation is universally available in UK.

Screen clipping taken: 20/02/2013 22:22

Nearly 70% reduction in cases since 2006 is attributable to the immunisation program. Given that millions of GP visits are children, the fact is the chance of any one GP diagnosing a case of meningococcal disease is vanishingly small today. Thus the hazard referred to is scaremongering. The British public deserve better information to make decisions about their kids who develop fevers and blanching rashes. Sadly a reputable charity, The Meningococcal Foundation perpetuates the hazard speculating there are nearly 3,500 cases of meningococcal disease annually in Britain. The figure for 2012 is 443 recorded cases, and many are adults.

Childhood Asthma

Asthma in children is a common condition. General practitioners diagnose the condition regularly. It is a core competency of MRCGP curriculum to diagnose, treat, and manage asthma.

What we cannot do is make parents give the treatment as often as may be needed. We cannot make children and teens take their inhalers regularly. Important risk factor for poor asthma control in youngsters include: parents/carers who smoke, overcrowding, damp, dusty environment. Prematurity is an independent risk factor for bronchial hyperreactivity/asthma. This is important with the upsurge in assisted conception and attendant increase in multiple births which often end in premature delivery of the babies.

Asthma UK does a good job helping people with asthma understand their condition and manage it properly, including an excellent section on inhaler usage.

Screen clipping taken: 20/02/2013 22:36

It is not doctors’ fault that many children have poorly controlled asthma and asthma-like conditions. People with asthma must take more responsibility for the correct management of this long term condition. Wringing of hands that doctors are not treating people with asthma properly perpetuates a State-controlled solution for every ill affecting individuals. This requires better reading comprehension, better education of children to take responsibility for their actions/conditions, and better access to online resources for everyone to improve information flow.

The story about asthma can apply to every long-term condition. There is not space here to enumerate many of the places to look for advice, though NHS Choices and BBC Health deserve wider readership at least in UK.

Minor illness admissions of children

It is a truism that all serious illness begins as minor illness. The trick is to spot which cases may progress. Doctors receive many years of training to learn how to spot the the worrying case. It is an art not a science in this. Suffice to say, like many of my colleagues, I will refer a child to hospital when I fear that worry will stop me sleeping at night about a particular case. This is, I know, not scientific, but when the hairs on the back of my neck stand on end, the child in front of me at that moment will be referred to see a colleague in paediatrics.

If one admits too few patients to hospital, too many unwell children will be taken to Emergency Department out of hours. If one admits too many children, there will be no space for the truly ill child referred by a colleague. All GPs know this. Yes some of us are high referrers while others are not. No-one has discovered what is the ideal referral rate. This is well known to the profession and health economists.

Therefore the accusation in the article is baseless.

Prescribing untested drugs to children

This is a specious argument. With the widespread availability of the British National Formulary for Children, there is a sound basis for prescribing for children in UK (and elsewhere). Yet another baseless accusation threatening to undermine the professionalism of the medical profession in its management of children.

Too few GPs have postgraduate child health training

This is baseless accusation too. General practice curriculum described by RCGP includes core competency in child health. Further, nearly 80% GPs have some postgraduate training in paediatrics before they complete general practice training (at least in UK) [personal communication from Doctors.net website].


The British public has a fantastic primary healthcare service which serves our children well. With a little bit of research it is obvious the article which prompted me to write this is full of inaccuracies and unfounded accusations.

The doctor will see you now… if you are truly ill.

31 Jan

Why is everyone scared of missing cancer? [BBC Radio 4 PM, 30-Jan-2013]

Personally public needs to (wo)man up and face the fact we die. And most of us die from heart disease or lung disease.

Doctors know, though many politicians and public do not, that early diagnosis of cancer often fails to prolong life of patient. For example, read Prof Baum opinion about breast cancer screening

Medical industrial complex loves us diagnosing cancer early because lots of tests, procedures, and drugs will be thrown at the poor patient for “extra” disease free months/weeks. Has anyone stopped to check the ROI for the vested interests in the management of people who are diagnosed early?

Meanwhile, earlier diagnosis of depression may be useful though you know that many people with “affective disorders” and other psychiatric c condition’s are also a construct of the medical industrial complex – DSM V is an opportunity to medicalise more situations that are part of normal living.

Perhaps, earlier diagnosis of erosive arthropathy may have benefits for sufferers. This population of patients is tiny compared with cardiac and respiratory and psychiatric patients.

So to cardiac and respiratory disease.  If the politicians are to be believed, people with BMI 19-25 who never smoke will not develop heart or lung disease.  This is magical thinking. One patient at my cardiac rehabilitation class who was thin, young, with cholesterol < 4 and no family history of heart disease, and never smoked.  Apparently cardiac rehabilitation clinics see significant number of such people.

Sadly there are a large number of people with chronic lung disease who never smoke – many of these people have asthma. Even with good inhaler use and compliance, many of these people will develop COPD which is supposed to be a disease of smokers only.

So in spite of the propaganda, seeing your doctor at your time and choosing is actually not going to save your life.  Remember healthchecks are useless. Thus, the media and many public voices should stop whinging about access to primary care and GPs.

29 Dec

Thank you to Nick Bennett [@peds_id_doc] Assistant Professor in Pediatric Infectious Disease for permitting me to repost here.

The message:  many febrile illnesses in our [Western – developed country] community are due to viruses for which there are generally no effective treatments. If you or your children have a fever it may last up to three weeks and this is not affected by the use of oral antibiotics. So, in almost all cases treat the symptoms – fever control, pain management, light diet with plenty of fluids. [A Cochrane review for basis of this approach in case of respiratory tract infectionshttp://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004417.pub3/full]

culture and sensitivity

I joke that, as a Peds ID doc, it is my duty to say this at least once a day…


Ok, I may not literally be slapping people upside the head, but there are certainly times when I’m doing it in my mind. The situation is common enough – a patient, parent or doctor, faced with symptoms consistent with an infectious disease, considers using antibiotics to treat bacteria. After all, we know that bacteria kill people, right? But in many of these situations the patient really has a viral infection – and viruses aren’t affected by antibiotics. So at the very least we’re wasting money and drugs. Worst case scenario? We’re promoting drug-resistant bacteria, antibiotic allergies and side effects – that in some cases can be life-threatening.

But aren’t there clues to help us make the distinction? Real clinical signs and symptoms? Well, lets review a few.

White pus on…

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