Author: piredda laura
Date: 06/05/2009



Hypothyroidism is a morbid condition caused by a lack of thyroid hormones (T3 and T4) or a lack of their effect on target tissues (TH resistance), dependent on genetic factors or competition for RXR by different hormones (eg. glucocorticoids , 1,25(OH)2VitD etc)

The disease definition according to a specific consensus conference or to The Diseases Database based on the Unified Medical Language System (NLM)

The Diseases DatabaseHypothyroidism


The hypothyroidism is commonly in the elderly. The increased frequency is observed in women. Prevalence over 60 years is the 1.5-2%.
It may already be present at birth and determine, if not promptly treated, serious problems of intellectual and physical development (cretinism sporadic), now easily preventable through the tests that are found all the babies to see if their thyroid is well developed during the pregnancy and especially function normally at birth (neonatal screening of hypothyroidism)
Thanks to improved social conditions and health, a diet richer and more balanced - even with the use of iodized salt (iodine prophylaxis) - Neonatal screening and advances in the diagnosis and treatment of thyroid diseases, today these serious forms of hypothyroidism in early childhood onset are actually missing.
Remains very frequently hypothyroidism in:

  • children of school age
  • adolescents
  • adults

In these cases the hormonal deficiency appears in a body already more or less fully developed, particularly in the brain, and therefore does not give cretinism. Are present goiter other disorders more or less severe. If not properly treated, hypothyroidism can impair the efficiency of the whole body.
The disease is found:

  • Europe
  • North America
  • Nepal
  • New Guinea
  • Zaire

In some countries, including Italy, hypothyroidism from lack of iodine in the diet is still quite common, even in children and adolescents. Over 10 million Italians are suffering because of goiter endemic iodine deficiency. One problem not yet solved, so that was recently approved by Parliament a law to encourage the consumption of iodized salt in place of common table salt. The use of salt enriched with iodine in the preparation and storage of foods is an effective form of prophylaxis of endemic goiter.


Symptoms affect all the organs because they are all
sensitive to hormone (Symptoms)

In some ways the most serious one has the so-called facies myxedematosa, resulting in swelling of the face and is due mainly to an increase of interstitial fluid in skin tissue.
The myxedema is a hard swelling which can affect:

  • mouth (swelling)
  • vocal cords (deterioration of the voice becomes throaty)
  • skin and appendages (hair loss, dry skin)
  • yellowing of the skin (palms of the hands and soles of the feet).
  • goitre may be present, if the cause is due to an altered synthesis of thyroid hormones, for example, to lack of iodine. In some patients the goitre disorders may give local compression, especially if you have retrostenal extension. In this case you can have compression and displacement of the trachea or esophagus, the patient complains of difficulty swallowing solid foods.

Myxedema coma

It’s a serious medical condition that appears rarely, is exceptionally the final stage of hypothyroidism, occurs most often after prolonged exposure to cold, infections and trauma, or following ingestion of sedative drugs.

  • slowed heart rate
  • hypothermia (body temperature below 34 ° C)
  • somnolence gradually until coma.
  • cardiomegaly
  • bradycardia
  • abnormalities of the genital tract, with decreased libido in men and women, and abnormal menstrual cycle
  • muscle fatigue
  • alterations of the skeleton (hypothyroidism occurs during childhood)


The symptoms are not sufficient to make diagnosis, but must be used at a dose of thyroid hormones.
Laboratory tests:

  • thyroid hormone dosing: FT3 and FT4 (reduced); thyrotropin, TSH (increased)
    In patients where there is evidence of low FT4 and normal or low TSH, you should seek a secondary hypothyroidism with interest then of hypothalamus and pituitary. In this case the tests are made more complicated, one of which is the Test to TRH
  • antithyroid antibodies: antithyreoglobulin and antiperoxidase to search for an autoimmune involvement, as in thyroiditis.
  • complete blood count:hypercholesterolemy, anaemia (reduction of hemoglobin values)








Stress dependent high serum cortisol

StressHacker: Towards Practical Stress Monitoring in the Wild with Smartwatches. 2018

Elevated thyroid stimulating hormone is associated with elevated cortisol in healthy young men and women. 2012

    Recent attention has been given to subclinical hypothyroidism, defined as an elevation of TSH (4.5-10 uIU/L) with T4 and T3 levels still within the normal range. Controversy exists about the proper lower limit of TSH that defines patients in the subclinical hypothyroidism range and about if/when subclinical hypothyroidism should be treated. Additional data are needed to examine the relationship between markers of thyroid function in the subclinical hypothyroidism range, biomarkers of health and ultimately health outcomes.
    We aimed to assess the relationship between serum TSH levels in the 0.5-10 uIU/L range and serum cortisol in a cohort of healthy young men and women without clinical evidence of hypothyroidism. Based on data in frank hypothyroidism, we hypothesized that serum TSH levels would be positively correlated with serum cortisol levels, suggesting derangement of the cortisol axis even in subclinical hypothyroidism.

We conducted a cross sectional study in 54 healthy, young (mean 20.98 +/- 0.37 yrs) men (19) and women (35). Lab sessions took place at 1300 hrs where blood was drawn via indwelling catheter for later assessment of basal serum TSH, free T3, free T4, and cortisol levels.

All but 1 participant had free T3 levels within the normal reference intervals; free T4 levels for all participants were within the normal reference intervals. Linear regression modeling revealed that TSH levels in the 0.5-10 uIU/L were significantly and positively correlated with cortisol levels. This positive TSH-cortisol relationship was maintained below the accepted 4.5 uIU/L subclinical hypothyroid cutoff. Separate regression analyses conducted by systematically dropping the TSH cutoff by 0.50 uIU/L revealed that the TSH-cortisol relationship was maintained for TSH levels (uIU/L) ≤4.0, ≤3.5, ≤3.0, and ≤2.5 but not ≤2.0. Linear regression modeling did not reveal a relationship between free T3 or free T4 levels and cortisol levels.

Results suggest a positive relationship between TSH and cortisol in apparently healthy young individuals. In as much as this relationship may herald a pathologic disorder, these preliminary results suggest that TSH levels > 2.0 uIU/L may be abnormal. Future research should address this hypothesis further, for instance through an intervention study.

Social stress-induced hypothyroidism is attenuated by antidepressant treatment in rats. 2012

  • Abstract

Although serotonergic system has been classically implicated in mood modulation, there has been relatively little study on the relationship between this system and thyroid hormones (TH) economy in stress models. When TH are studied, the effects of stress on thyroid function seems to be complex and depend on the kind and time of stress which counts for the elusiveness of mechanisms underlying changes in TH economy. Herein, we hypothesized that serum TH are affected in a time-dependent fashion after repeated social stressful stimuli and serotonergic system is implicated in these changes. Therefore, we aimed to investigate the possible alterations in thyroid hormone economy and type 1 (D1) and type 2 (D2) deiodinase activity in a model of social defeat stress. Thereafter, we tested the responsiveness of these changes to fluoxetine treatment. Both short (STS) and a long-term (LTS) stress were performed. Blood samples were drawn just before and 1 (STS) or 4 and 8 weeks (LTS) after the beginning of stress to assess serum T4, T3 and corticosterone. Deiodinases activity was assessed at the end of each protocol. Stress-induced behavior studied in open field arena and hypercorticosteronemia were mainly observed in LTS (week 4). Stress-induced behavior was associated to hypothyroidism which occurred before, since week 1 in stressed group. Serum TH was restored to control levels in week 8, when behavior changes were not observed anymore, and was mainly associated with high brown adipose tissue D2 activity since thyroid and liver D1 activity were low or normal in the STS and LTS respectively in stressed rats compared to control. Antidepressant study revealed that fluoxetine treatment (10mg/kg po during four weeks) fully reversed stress-induced behavior and normalized serum T4, but not T3 levels and hypercorticosteronemia in stressed group compared to control. The current work adds new concepts concerning TH metabolism changes induced by social stress and suggests that serotonergic system impairment may take part in the key events which ultimately lead to hypothyroxinemia and behavioral changes induced by chronic social defeat. This article is part of a Special Issue entitled 'Anxiety and Depression'.


anatomical (due its structure)

vascular (due to the local circulation)

physiopathological (due to tissue function and activity)


The system includes hypothalamus -> pituitary -> thyroid -> liver -> receptors
tissue (muscle, liver, heart etc) any alteration in one of these points induces different disease:

  • hypothalamus and pituitary
    • mutated gene for the hypothalamic receptor -> thyroid hormones act through negative feedback on hypothalamus and pituitary tying a subtype of THRB that could be mutated
    • levels of thyroid hormones slightly subnormal -> increase secretion of TSH from the pituitary gland
    • lesion -> hormone insufficient respectively TRH and TSH hormone, resulting in reduced incentives for the production of thyroid hormones (secondary hypothyroidism)
  • thyroid
    • development of congenital deficiency of thyroid gland -> at birth there is a reduced mass of thyroid tissue; during fetal life and neonatal deficiency of thyroid hormones causes a developmental delay of the central nervous system
    • autoimmune processes -> body due to an infection of the thyroid (Hashimoto thyroiditis) produces antibodies against its own thyroid tissue. The thyroid gland becomes fibrotic and has a low volume, the synthesis function is impaired.
    • post-treatment -> reduction of thyroid tissue due to thyroid surgery or radiation therapy with radio-iodine, used in hyperthyroidism; also use of drugs antithyroid
    • iodine deficiency, or intake of high amounts of iodine in the form of drugs (it's content, for example, in the cough syrups) or dietary supplements.
    • selenium deficiency
    • changes in the proteins necessary for synthesis of biochemical processes of thyroid hormones
  • lack of conversion of T4 to T3 in the liver, but is not documented in humans or animals. Low T3 with normal T4 values are often due to concomitant disease (euthyroid syndrome) or administration of drugs:
    • amiodarone
    • lithium
    • propranolol
    • corticosteroids
    • contrast media iodates



04. TSH normal range 0.5-4.5 ????


Thyroid Hormone Replacement Therapy

Patients info

Hypothyroidism overview at endocrineweb
Laura Piredda e Marzia Pera

2022-06-02T21:25:39 - Gianpiero Pescarmona

Hypothyroidism is often associated with Vitamin B12 deficiency

Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective study. 2017

Objective: To investigate the association between pernicious anemia and other autoimmune diseases. Methods: This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome. Results: A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b. Conclusion: We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b.

Thyroid function and autoimmunity in pernicious anemia before and during cyanocobalamin treatment. 1995

Out of 35 consecutive patients with decreased plasma-cobalamin 22 had newly diagnosed overt pernicious anemia (PA) six of which had a known history of thyroid disease. At referral, 5 of these 6 were thyroid peroxidase antibody (TPOAb)-positive and 2 were thyroglobulin antibody (TgAb)-positive, while none were thyroid stimulating antibody (TSAb)-positive (an overall autoantibody appearance of 83.3%). Fifty percent of the 22 patients had TPOAb and 13.6% had TgAb compared to 18.2% and 4.5%, respectively in sex and age matched healthy controls. Six PA-patients without a history of thyroid disease had thyroid autoantibodies and another patient seroconverted within the first year during treatment with cyanocobalamin. Measurements of serum concentrations of thyroid hormones and thyroid stimulating hormone were performed during the first year of treatment with cyanocobalamin. Two cases of subclinical myxoedema were found among PA-patients and another case was found among patients with latent PA. The female:male ratio of thyroid disease among PA-patients and among thyroid autoantibody-positive PA-patients was interestingly found to be 1:1. Treatment with cyanocobalamin did not have any systematic effect on thyroid function. Routine screening for thyroid function and thyroid autoantibodies in patients with latent or overt PA is recommended.

Prevalence of vitamin B-12 deficiency among patients with thyroid dysfunction. 2016

Collins AB, Pawlak R.
Asia Pac J Clin Nutr. 2016;25(2):221-6. doi: 10.6133/apjcn.2016.25.2.22.
PMID: 27222404 Free article. Review.
Autoimmune thyroid disease is also associated with the autoimmune disorders pernicious anemia and atrophic gastritis which may lead to malabsorption of vitamin B-12. Vitamin B-12 screening is recommended …

Iron Deficiency Predicts Poor Maternal Thyroid Status during Pregnancy
J Clin Endocrinol Metab (2007 September 01) 92(9): doi: 10.1210/jc.2007-1082
In hypothyroidism, ID may occur due to poor iron absorption secondary to achlorhydria (27, 28).

but it is not clear why:

Does Vitamin B12 deficiency depend on hypothyroidism or vice-versa?
apparently, Vit B12 supplementation is useless
Primary hypothyroidism, induces achlorhydria that impairs iron and Vit B12 absorption


hypothyroidism should be primary and vitamin B12 deficiency secondary.


What about infections of the teeth, mouth, or throat?
What about the stomach?
Estrogens and menstrual cycle (pill, ring?)
blood pressure and heart rate
Dietary antioxidants (green tea, etc)

Additional blood tests

serum cholesterol and HDL chol

2016-10-19T13:40:34 - Gianpiero Pescarmona

Common chemicals that can induce hypothyroidism


The proposed studies will provide evidence that thyroid hormone may act directly on the medullary nuclei related to autonomic function by regulating the synthesis and turnover of its neuropeptides and neurotransmitters and will yield substantive information on the mechanisms through which autonomic disorders participate in the clinical manifestations of thyroid diseases.

Small non-coding RNAs in animal development 2008

In normal conditions in wild-type animals, miR-208 maintains an optimal level of the thyroid hormone receptor (TR) cascade activity by acting on THRAP1 (thyroid hormone receptor-associated protein complex 240 kDa component) in a negative feedback loop. In transgenic mice that overexpress miR-208, inhibition of the TR pathways allows aberrant expression of beta-myosin heavy chain (betaMHC) in the adult. Similarly, in conditions of stress or hypothyroidism, decreased activity of the TR cascade leads to expression of betaMHC and hypertrophy. In the absence of miR-208 in null mice, THRAP1 is de-repressed and baseline levels of TR activity are abnormally high and resistant to inhibition by stress signals. Therefore, Mir-208-null mice do not express elevated levels of betaMHC or undergo cardiac hypertrophy in conditions of stress and hypothyroidism. T3, tri-iodothyronine; TRE, T3 response element.

Approach to mild hypothyroidism diagnosis

L'ipotiroidismo in Italia
L'ipotiroidismo congenito in Italia, 2009,Meeting ISS

DHEA albumin in hypothyroidism

Serum Dehydroepiandrosterone, Dehydroepiandrosterone Sulfate, and Pregnenolone Sulfate Concentrations in Patients with Hyperthyroidism and Hypothyroidism 2000

Effects of developmental hypothyroidism induced by maternal administration of methimazole or propylthiouracil on the immune system of rats. 2007

Anemia, ipotiroidismo subclinico e levotiroxina
I pazienti con anemia da deficit di ferro ed ipotiroidismo subclinico potrebbero richiedere il trattamento con ferro e levotiroxina. Vi � infatti una categoria di pazienti che non risponde bene al ferro per via orale proprio a causa della concomitante presenza di ipotiroidismo subclinico, e questi pazienti potrebbero trarre beneficio dall'integrazione della levotiroxina. In generale, questa condizione si osserva nel 17,2 percento dei casi. Gli ormoni tiroidei hanno un effetto diffuso nell'organismo, e minore � il livello dell'emoglobina, maggiore � l'effetto della combinazione ferro-levotiroxina. E' stato dimostrato anche che bench� la levotiroxina aumenti i livelli di eritropoietina, essa non incrementa quelli dell'emoglobina nei pazienti con ipotiroidismo subclinico non anemici. Sembra dunque che l'interazione fra ormone tiroideo, tireotropina e cellule non sia semplicemente un'estensione dei loro effetti fisiologici, ma che questi ormoni abbiano effetti d'organo unici sia a livello sistemico che cellulare, probabilmente sulla base dello status di deficit o eccesso. Sono in programma studi per investigare l'effetto di elementi quali selenio e zinco nel trattamento dei pazienti con ipotiroidismo subclinico e deficit di ferro. (J Clin Endocrinol Metab 2009; 94: 151-6)

Ipotiroidismo e tumori epatici nelle donne
Le donne con ipotiroidismo di vecchia data presentano un aumento del rischio di carcinomi epatocellulari, mentre ci� non si riscontra nel sesso maschile. E' noto che gli ormoni tiroidei sono coinvolti nel metabolismo lipidico, e vi sono prove di un legame fra ipotiroidismo e steatoepatite non alcolica, ma non era finora chiaro se i disordini della tiroide fossero associati ai tumori epatici. Sono ora necessari studi in popolazioni diverse per confermare l'associazione fra ipotiroidismo e carcinoma epatocellulare ed identificare i meccanismi biologici di base ed i fattori predisponenti che potrebbero contribuire alla suscettibilit� a questi tumori in presenza di disordini tiroidei. (Hepatology 2009; 49: 1563-70)

Rapporto tra ipotiroidismo, diabete e mortalit� Cv
L'ipotiroidismo subclinico (Is) � stato associato a una maggiore prevalenza di malattia cardiovascolare ed � di riscontro comune in pazienti con diabete di tipo 2 (Dm). Per indagare la veridicit� di questi dati clinici, � stata condotta un'ampia analisi retrospettiva su 6.540 soggetti, di cui 472 affetti da Dm e con un aumentato livello di Tsh, paragonati con 472 soggetti di pari et� con Dm e normali valori di Tsh. La relazione tra Is e mortalit� cardiovascolare � stata effettuata mediante regressione logistica. Si sono registrati 222 nuovi eventi cardiovascolari nei pazienti con Is rispetto a 246 eventi in pazienti senza. E si sono avuti 96 morti da tutte le cause nei pazienti con Is rispetto a 155 in quelli senza. Non si � avuta alcuna relazione tra il valore di Tsh iniziale e la mortalit� cardiovascolare. Nel complesso, i pazienti con Is e Dm non avevano una mortalit� cardiovascolare accresciuta rispetto ai pazienti con Dm senza Is. Inaspettatamente, si � avuta una riduzione significativa della mortalit� da ogni causa nei pazienti con Is e Dm. Questi dati sono in accordo con studi che mostrano che individui anziani con pi� alti livelli di Tsh hanno dimostrato una vita prolungata. In conclusione, l'Is pu� avere un effetto protettivo sulla mortalit� non-cardiovascolare nel Dm.

Diabetes care, 2010;33(3):e37

vitamin d eosinophils

vitamin d hypothyroidism

Diurnal hormone-metabolite profiles in hypothyroidism. 1981

Fasting blood lactate and pyruvate levels were normal but post-prandial hyperlactataemia and hyperpyruvicaemia were found and mean 12 h values for lactate (hypothyroid 1.80 +/- 0.06 v. control 0.77 +/- 0.03 mmol/l, P less than 0.01) and pyruvate (0.10 +/- 0.01 v. 0.08 +/- 0.003 mmol/l, P less than 0.01) were elevated.

Goiter iron deficiency - Results from Quertle®

Are human herpes viruses associated with autoimmune thyroid disease?

  • INTRODUCTION Autoimmune diseases are complex diseases with genetic, endogenous and environmental etiologies. Viral infections have been postulated as one of the factors that may be the trigger of autoimmune diseases.
    METHODOLOGY Thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies were measured before thyroidectomy in 100 subjects by chemiluminescence method, 50 of whom were autoimmune thyroid diseases (AITD) patients and 50 of whom were multinodular goiter (MNG) patients used as a control group. Fresh thyroid samples were collected from all 100 subjects after thyroidectomy to investigate the DNAs of herpes simplex viruses types 1 and 2 (HSV-1, HSV-2), Varicella Zoster virus (VZV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV) and human herpes virus type 6 (HHV-6) by PCR.
    RESULTS The DNA of HSV-1, HSV-2, VZV, EBV, CMV and HHV-6 were detected in neither the patient group nor in the control group. The mean values of anti-TPO and anti-TG antibodies ranged within 9.5-2000 units/ml (527.8 ± 617.4) and 108-5000 units/ml (1458.2 ± 1774.1) in the AITD patients group, respectively. A statistically significant difference of the mean level of anti-TPO and anti-TG antibodies among the two groups was found (p value < 0.05).
    CONCLUSIONS The possible role of human herpes viruses in the pathogenesis of AITD is not supported by our study; hence our raised question stays open for more investigation on more patients and in different parts of the country using different sizes and sites of biopsies.

Thyroid hormones and the hepatic handling of bilirubin. II. Effects of hypothyroidism and hyperthyroidism on the apparent maximal biliary secretion of bilirubin in the Wistar rat. 1988

  • Abstract
    This study was undertaken in the Wistar R/A Pfd rat to investigate the effects of hypothyroidism and of hyperthyroidism on the maximal biliary excretion ™ of bilirubin and on the concentration and composition of bilirubin in liver and plasma at the end of a bilirubin load. Hypothyroidism caused a cholestatic condition with a 50% decrease in bile flow and in bilirubin Tm, and with an increased proportion of conjugated bilirubin in liver and plasma. This was associated with an increased ratio of bilirubin diconjugates to monoconjugates in bile, liver, and plasma, which can be ascribed to the increased hepatic conjugation activity towards bilirubin and/or to the prolonged retention of bile pigments in the hepatocytes with increased conversion of monoconjugates to diconjugates. Cholestasis induced by hypothyroidism was further characterized by a decreased biliary output of unconjugated bilirubin. The latter phenomenon might represent an indirect effect related to a decreased output of bilirubin monoconjugates with impaired hydrolysis to unconjugated bilirubin; it might also reflect the cholestatic condition with decreased excretion of the unesterified bile pigment as such. Hyperthyroidism resulted in a 1.3-1.4-fold increase in bile flow. The maximal bilirubin concentration in bile decreased 1.3-1.4-fold, so that the apparent maximal bilirubin excretion rate remained unchanged at 115 nmol.min-1.100 g-1, as observed in untreated rats. Hyperthyroidism lowered the bilirubin UDP-glucuronosyltransferase activity, produced a decreased ratio of bilirubin di- to monoconjugates in bile and plasma, and a decreased ratio of conjugated to total bile pigment concentration in liver and in plasma. Similar findings are present in the heterozygous Gunn rat strain and in patients with hepatic bilirubin UDP-glucuronosyltransferase deficiency. We therefore propose the hyperthyroid rat as an experimental animal model of Gilbert's syndrome.








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