HASHIMOTO’S THYROIDITIS -THE RELEVANCE OF DIAGNOSTIC MODALITIES IN HOMEOPATHIC MANAGEMENT & A case study on the role of stress.

Introduction
Thyroid is one of the most important endocrine gland with its intricate metabolic pathways and complex hormone synthesizing mechanism. Thyroxine (T4) and triiodothyronine (T3), together referred to as thyroid hormones, play an important role in basal metabolism and the functioning of almost all tissues and systems in the body.
Untreated hypothyroidism can lead to increased body weight, cognitive dysfunction, fatigue, abnormal serum lipids, coronary heart disease, and recurrent miscarriage, infertility in women, and possibly delayed cognitive development in their children.
          Hashimoto’s thyroiditis [HT] or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is attacked by a variety of cell and antibody-mediated immune processes, ultimately causing primary hypothyroidism. It was the first disease to be recognized as an autoimmune disease. It was first described by the Japanese specialist Hakaru Hashimoto.
          The common symptoms of Hashimoto’s thyroiditis are fatigue, weight gain, edema, cold intolerance, joint and muscle pain, constipation, dry and thinning hair, heavy menstrual flow or irregular periods, depression, anxiety, bradycardia, infertility and recurrent abortions.   Hashimoto’s disease is about seven times more common in women than in men.  Although no age is exempt from the occurrence of the disease, it is commonly seen in middle-aged women. But of late there has been a significant rise in the number of adolescent male and female children affected with this auto immune disease. Our clinical data substantiates this fact. An observational study conducted at our clinics has found that apart from the genetic predisposition stress and lifestyle changes also have a key role.
         A family history of thyroid disorders is common, with the HLA DR5gene most strongly implicated. In addition Hashimoto’s thyroiditis may be associated with CTLA 4(Cytotoxic T-lymphocyte Antigen-4) gene polymorphisms.Our clinical observation  shows that thyroiditis in adolescent children is often associated with family history of the disease in mother or maternal relatives. It is found mostly in introvert children who had either a positive hereditary predisposition or extreme stress. In adolescent girls the disease has caused precautious puberty and development of secondary sex characteristics at an early age. Lifestyle changes and dietary changes also can be attributed to it.
          There are multiple suggested mechanisms by which the pathology of Hashimoto’s thyroiditis is evolved.
Various auto antibodies may be present against thyroid peroxidase, thyroglobulin and TSH receptors. Antibody-dependent cell-mediated cytotoxicity also plays an important role.
LITERATURE REVIEW – on the role of stress
Stojanovich L1, Marisavljevich D.
[Author information]
The etiology of autoimmune diseases is multifactorial. Genetic, environmental, hormonal, and immunological factors are all considered important in their development. Nevertheless, the onset of at least 50% of autoimmune disorders has been attributed to “unknown trigger factors”. Physical and psychological stress has been implicated in the development of autoimmune disease, since numerous animal and human studies demonstrated the effect of sundry stressors on immune function. Moreover, many retrospective studies found that a high proportion (up to 80%) of patients reported uncommon emotional stress before disease onset. Unfortunately, not only does stress cause disease, but the disease itself also causes significant stress in the patients, creating a vicious cycle. Recent reviews discuss the possible role of psychological stress, and of the major stress-related hormones, in the pathogenesis of autoimmune disease. It is presumed that the stress-triggered neuroendocrine hormones lead to immune dysregulation, which ultimately results in autoimmune disease, by altering or amplifying cytokine production. The treatment of autoimmune disease should thus include stress management and behavioral intervention to prevent stress-related immune imbalance. Different stress reactions should be discussed with autoimmune patients, and obligatory questionnaires about trigger factors should include psychological stress in addition to infection, trauma, and other common triggers.
Clinical presentations of Hashimoto’s thyroiditis to illustrate the role of diagnostic tools:
[From  data base of HV MULTISPECIALITY CLINIC]
        The clinical spectrum varies widely in the affected population.  It is a known fact that Hashimoto’s thyroiditis is classified in three stages-initial phase of mild hyperthyroidism followed by euthyroidism and finally sinking into permanent hypothyroid state due to follicular destruction. But clinical experience shows that duration this sequence of events varies with people affected. Most often symptomatic patients are euthyroid for many years and on primary screening with TFT, being euthyroid these patients are excluded from thyroid dysfunction and categorized under some other systemic diseases. This situation is confronted in clinics when a patient has no thyroid swelling and euthyroid on TFT and presenting with vague symptoms of fatigue, myalgia and hair loss which can have multifactorial causations. This article aims at exploring the wide clinical spectrum of Hashimoto’s thyroiditis with a renewed focus on it.
Hashimoto’s thyroiditis can present with mild hyperthyroidism, subclinical hypothyroidism, euthyroidism and overt hypothyroidism. Mild hyperthyroid state is seen in the initial phase of active thyroiditis. Later euthyroidism follows. Unfortunately in many patients this phase is prolonged for years with varied symptomatology .Some patients can have the typical symptoms of thyroid dysfunction while in others symptoms are vague and mislead the clinician as the patient is euthyroid on TFT. If proper intervention is not done at the right time this euthyroid patients can progress to overt hypothyroidism. A few clinical presentations of Hashimoto’s thyroiditis are mentioned below:
·         An adolescent male presented with mild hair fall and lack of concentration in studies. NO thyroid swelling or other symptoms and signs of thyroid dysfunction were noticed. TSH showed mild deviation from normalcy being border line. Later anti TPO antibody testing and sonography confirmed it as lymphocytic thyroiditis.
·         A middle aged woman presented with recurrent stomatitis and oral candidiasis was diagnosed by scrapings. she was treated by other school of medicine with antifungal medications. The only symptom she presented apart from oral candidiasis was anxiety about disease. She suspected it as carcinoma tongue and demanded repeated testing at laboratory although it was confirmed as oral candidiasis. TSH was tested as she had extreme levels of anxiety. Well selected homeopathic drugs failed to cure her oral candidiasis and anxiety .Then it was found out the lady had very low level of thyroxines. Homeopathic medicinal management having action on thyroid raised the hormone levels and cured her oral candidiasis permanently.
·         A middle aged woman presented with severe hair loss and obesity. She was tested for thyroid dysfunction earlier by other physicians and was diagnosed as euthyroid. She had no thyroidomegaly or palpable nodules. So hair loss was attributed to other causes. Sonography of thyroid revealed benign nodules and later fnac and anti TPO titer confirmed the disease as chronic lymphocytic thyroiditis.
·         Another presentation was lichen planus on the palms [as yellow powder like lesions] in a 50 years old lady with Hashimoto’s thyroiditis and she was on hormonal therapy for thyroid dysfunction for a few years. Her TSH was kept below 0.3 by medications as usually happens in other school of medicine .she was advised to withdraw hormonal supplements and Lycopodium 1m one dose was prescribed.  Within a week she was cured of lichen planus. Here lichen planus can be attributed to iatrogenic causes. In this case two things draw our focus of attention. The presentation of lichen planus can be iatrogenic or being an autoimmune disease it has co existence with thyroid diseases. The literature review of the possible link of oral lichen planus and Hashimoto’s thyroiditis shows that there are some studies which points to an association although the conclusion demands extensive studies in future to unravel the possible mechanism.
·          Hashimoto’s thyroiditis increases the risk of developing a number of autoimmune disorders like Addison’s disease, Graves’ disease, premature ovarian failure, type 1 diabetes, lupus erythematosus, pernicious anemia, rheumatoid arthritis, thrombocytopenic purpura, and vitiligo.
·         Hashimoto‘s thyroiditis can cause recurrent abortion in women. Research studies show that hypothyroidism and sub clinical hypothyroidism in women interfere with fecundity and cause miscarriage. In 2004, Prummel & Wiersinga published a meta-analysis of both the case-controlled and longitudinal studies. The results of this meta-analysis amply confirmed that an association exists, with an overall increased relative risk of a miscarriage of 2.73 in women with AITD. Several clinical studies have investigated the psychological and intellectual outcome in the offspring of pregnant women with thyroid insufficiency, both in conditions of hypothyroidism with an adequate iodine nutritional status and women with mild-moderate iodine deficiency. Overall, the results show that there is a significantly increased risk of impairment in neuro-psychological developmental indices, IQ scores, and school learning abilities in the offspring of untreated hypothyroid mothers.
·          Rarely Hashimoto’s thyroiditis shows coexistence of thyroid lymphoma. Hence   HT has to be followed regularly. This is mentioned here not for over diagnosing HT or advising surgery in all cases. But any change in thyroid sonography has to be taken seriously in HT patients. It mandates follow up of HT patients beyond TSH testing, using more sophisticated diagnostic tools especially in the older age group.
·         Another presentation of Hashimoto’s thyroiditis is its coexistence with Hurthle cell adenoma and carcinoma. A case from our clinical data illustrates it well. An obese lady teacher with recurrent hoarseness and uniformly enlarged thyroid who had history of gestational diabetes and post partum thyroiditis consulted us with a border line TSH [5.1mIU]. Sonography diagnosed it as hashimoto’s thyroiditis with a few lymph node enlargement .FNAC detected the presence of a coexisting Hurthle cell adenoma and Hashimoto’s thyroiditis. This example poses questions before a clinician about the management, if surgery needed or homeopathic treatment sufficient to cure. Although FNAC is gold standard in thyroid diagnosis false negative and false positive results can’t be avoided in all variants of thyroid neoplasms. How can we differentiate Hurthle cell adenoma from Hurthle cell carcinoma at cytological level? We know that histopathology after surgery can detect many carcinomas as benign and vise versa. But to avoid an unnecessary surgery it has to be assessed with sonography and FNAC [CYTOLOGIOCAL STUDY].Hashimoto’s thyroiditis on FNAC smears is diagnosed by presence of Hurthle cells, infiltration of follicles by lymphocytes or plasma cells and the presence of moderate amount of colloid in the background.FNAC is superior to antibody screening [anti TPOab] in diagnosing HT.Cytological features favoring the diagnosis of HASHIMOTO’S THYROIDITIS over neoplasms [Hurthle cell carcinoma and adenoma] are absence of poorly organized cell clusters having nuclear pleomorphism [ i.e, Anisonucleosis of Hurthle cells ]. Epithelial preponderance, nuclear crowding, cytological atypia and cell discohesion should raise the possibility of a neoplasm inspite of having other features of HASHIMOTO’S. It suggests a coexisting malignancy. Hurthle cell carcinomas consists of at least 75% of Hurthle cells, shows vascular and capsular invasions.
ROLE OF RT3 DOMINANCE IN HASHIMOTO’S THYROIDITIS AND EFFECT OF HOMEOPATHIC MEDICINES IN REVERSING THE CHANGE
   T3 is the active thyroid hormone and every cell in the body has molecular docking stations for T3.
T4 is made by the thyroid, circulates and eventually ends up in the liver where it is converted to T3 and a tiny amount of a substance called Reverse T3 (RT3). RT3 has no action on the cell, except that it binds with the receptor sites, and blocks the action of T3. However, in the normal situation, T3 dominates and RT3 is no problem.
However, when a person experiences prolonged stress, the adrenal glands respond by producing a large amount of cortisol. Cortisol inhibits the conversion of T4 to T3 and favors the conversion of T4 to RT3. If stress is prolonged, a condition called Reverse T3 Dominance occurs and persists even after the stress passes and cortisol levels fall. Apparently, RT3 itself acts like cortisol and blocks the conversion of T4 to T3. Reverse T3 Dominance is the cause of hypo metabolism because too many receptor sites are blocked by RT3 and the chemical reactions of life slow down. This is because the reverse T3 continues to inhibit the conversion of T4 to T3, perpetuating production of the inactive T3 hormone. Prolonged stress is the major cause of reverse T3 dominance. Reverse T3 has the same molecular structure as T3 however it is a mirror image of T3 and therefore fits into the receptor upside down. This prevents the active T3 from binding to the receptor site and activating the appropriate thyroid response Reverse T3 slows metabolism and causes the typical signs & symptoms of hypothyroidism.
A specific measurement of reverse T3 is valuable in identifying excessive levels of reverse T3 —Reverse T3 Dominance.
High levels of stress, toxicity, adrenal exhaustion, hypoglycemia and/or low sex hormone levels are the key factors that lead to reverse T3 dominance.
Stress factors increasing cortisol levels
· Viral infections increase cortisol levels through activation of the HPA axis by cytokines.
· Caffeine may increase cortisol levels.
· Sleep deprivation
· Intense or prolonged aerobic exercise transiently increases cortisol levels to increase gluconeogenesis and maintain blood glucose; however, cortisol declines to normal levels after eating
· Severe trauma or stressful events can elevate cortisol levels in the blood for prolonged periods.
· Subcutaneous adipose tissue regenerates cortisol from cortisone by the enzyme 11-beta HSD1.
· Anorexia nervosa may be associated with increased cortisol levels.
· The serotonin receptor gene 5HTR2C is associated with increased cortisol production in men.
· Severe calorie restriction causes elevated baseline levels of cortisol.
RESEARCH PROBLEM:
Can homeopathic medicines alter the neuro-immuno-endocrine modulations of thyroid resulting from stress?
NULLHYPOTHESIS:
Homeopathic medicines do not make any change in altering Anti TPO titer or TFT.
Materials and methods: clinical trial
Inclusion criteria: patients having anti TPO titer positivity and FNAC positivity for Hashimoto’s thyroiditis of age group 10 to 50 years.
Exclusion criteria: patients with no apparent thyroid illness, pregnant &lactating women, old people, psychiatric patients, neonates excluded.
The study is not subjected to statistical analysis as this is planned as a pilot study with small sample size. [An extensive study in future with ample sample size and bias free instrumentation is planned]
Clinical findings:
Homeopathic medicines which have found to be effective in clinical practice in the order of maximum effectivity are:
Natrum muriaticum 1M and higher potencies
Lycopodium 1M
Baryta muriatica 200
Calcarea carbonica 1M
Bromium 1M
Calcarea fluorica 200
Thyroidinum 3x
Compared to the conventional medical hormone therapy with levothyroxine which helps only in achieving euthyroid state homeopathic medicines could achieve euthyroid state along with better quality of life with respect to their physical and mental symptoms.
The extra benefit of homeopathic treatment include the following
·         Emotional stability
·         Reduced sleepiness
·         Liveliness and quality of life improved.
·         Reduced oedema, dryness of skin, reduced hair loss.
Lab findings:
After treatment an apparent increase in T3 AND T4 was noticed with the symptomatic recovery. It was evident with respect to T3 bcoz many symptomatic patients who had subclinical or overt hypothyroidism had low T3 Level compared to t4.As we mentioned earlier T3 is the biologically active thyroid hormone although T4 is the determinant of hypo or hyperthyroidism in clinical diagnosis.
All these point out that the metabolic slowing due to T3 reduction is positively altered by homeopathic medicine. 
Conclusion:
In the study population it has shown to alter the anti TPO ab titre positively among younger age group. There has been remarkable change in TFT status in younger age group with Hashimoto’s thyroiditis. HASHIMOTO’S thyroiditis being an autoimmune disease having multifactorial causation and having various explanations for the pathogenesis we find stress as one of the multiple factors causing the disease in genetically susceptible populations. The role of cortisol and RT3 in slowing down metabolism needs further extensive research for finding out a solution to alter the RT3 dominance which persists despite cortisol withdrawal .We want to study the effects of a few homeopathic medicines in reversing RT3 DOMINANCE and thus making biologically active T3 available for metabolic functions to establish euthyroid state.
 It needs extensive research in future in altering
1] Anti TPO ANTIBODY levels,
2] Cortisol and negative feedback with TSH,
3] T3, reverseT3 conversion
4] receptor level action of  homeopathic medicines.
Reference:
[literature review section]
[reference- from our clinical data base- HV multispeciality homeopathy clinics]
http://www.ncbi.nlm.nih.gov/pubmed/15650357
http://www.ncbi.nlm.nih.gov/pubmed/18190880
https://www.nlm.nih.gov/medlineplus/ency/article/000371.htmwikipedia—-
https://en.wikipedia.org/wiki/Hashimoto%27s_thyroiditis