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Updated treatment of hypothyroidism

Updated treatment of hypothyroidism

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Updated treatment of hypothyroidism

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  1. Updated treatment of hypothyroidism Professor / Mohammed Ahmed Bamashmos

  2. Prevalence Of overt hypothyroidism Of subclinical

  3. Classification

  4. Causes

  5. Causes of SCH ; - Autoimmune ( Hash motoes thy - suboptimal treatment of overt hyperthyroidism - partial thyroidectomy - radioactive iodine ablation -radiation -drugs ( iodine contrast , amiodarone , lithelium , tyrosine kinase - iodine deficiency or excess Causes of hypothyroidism during pregnancy ; ( 5% - Hashimotos diseases ( it occurs in 2 to 3 out of 100 pregnant ) - iodine deficiency - overtreatment of hyperthyroidism

  6. Adverse effect of hypothyroidism if not treated A- overt hypothyroidism ; Untreated hypothyroidism can lead to serious mental and physical health problems. Complications of untreated hypothyroidism can include the following. 1-Mental health changes Hypothyroidism affects your mind as well as your body. It can slow your thoughts, make you forgetful, and affect your ability to concentrate. In fact, hypothyroidism is one of the reversible causes of dementia.  more mood swings and irritability. People with hypothyroidism might be more likely to have anxiety and depression. If you already suffer from depression, being hypothyroid can make it harder to treat.  2- Goiter 3- CVD ( HF, CAD ) 4- Nerve damage ( pain , numbness , muscle weakness of upper limb ) 5-myxedema coma 6- infertility 7- effect on pregnancy

  7. B- Adverse effect of SCH ;

  8. C- Adverse effect of Gestational hypo Effect on mothers - risk of premature birth - low birth weight - miscarriage - gestational hypertension - preeclampsia - post partium hemorrhage - myopathy Effect on the fetus - cognitive impairment - neurological abnormalities - congenital hypothyroidism

  9. SCREENING Indication ; A- In pregnant women with history of - family history , thyroid diseases during pregnancy , complicated pregnancy , recurrent miscarriage , positive ATP - Menstrual irregularities B- Any patients with history of - unexplained stunted growth - CNS ( Dementia , other psychiatric - CVS ( CVD , Dyslipidemia - Menstrual irregularity , infertility C- Any patients with 4 or more of the following symptoms ; - fatique , coldness , goiter , dry skin , weight gain , constipation

  10. Diagnosis 1- to diagnose hypothyroidism ; A - measurement of TSH ; its most sensitive test Important ; - diagnose all types of hypothyroidism - monitoring response to therapy in primary , SCH , GH Other cause of false increase - physiological increase - Diurnal variation - Recovery phase of euthyroid sick syndrome - recovery phase of subacute , painless or postpartum - other causes - Assay variability - Substance that interfere with TSH assay ( heterophil Abs , RF , Biotin , macro TSH - Impaired RF

  11. B- FT3,FT4 - Diagnosis of overt hypothyroidism - differentiate overt from subclinical - to determine the response to therapy in secondary 2- to know the cause ; A- in congenital ;

  12. B- Acquired 1- primary ;

  13. Other investigation - urine iodine - RAIU -Neck U/S Diagnosis of hypothyroidism during pregnancy Hypothyroidism is the most common pregnancy-related thyroid disorder, affecting 3–5% of all pregnant women. Subclinical hypothyroidism is more common than is overt hypothyroidism, and is usually defined as a serum thyroid-stimulating hormone (TSH) concentration greater than the pregnancy-specific reference range for each laboratory value, or by serum TSH concentrations greater than 2·5 mIU/L in the first trimester and greater than 3 mIU/L in the second and third trimesters.

  14. diagnosis ; If available, trimester-specific reference ranges for serum TSH should be used for interpretation of thyroid function tests during pregnancy.31, 32, 33 If trimester-specific reference ranges for TSH are not available in iodine-sufficient regions, the following upper normal reference range limits are recommended: 2·5 mIU/L for the first trimester, 3·0 mU/L for the second, and 3·0–3·5 mIU/L for the third.1, 34 At present, assessments of FT4 are the most controversial

  15. Diagnostic algorithm

  16. Treatment ; 1- levothyroxine ; it’s the slandered goal for treatment of hypothyroidism regardless of the cause because of - Levothyroxine indication ; - In congenital hypothyroidism - In acquired ( primary , secondary , tertiary ) - in transient - In subclinical - In gestational hypothyroidism - levothyroxine has FDA approval for pituitary thyrotropin suppression as an adjunct to surgery and radioiodine therapy to manage thyrotropin-dependent well-differentiated thyroid cancer.[3] -  Injectable levothyroxine is FDA approved for the treatment of myxedema coma or severe hypothyroidism.

  17. benefit ; its indicated in all types and cause of hypothyroidism - it induce clinical Precaution before administration ;

  18. levothyroxine dose ; 1- Assessment of risk factors ;

  19. factors that should be considered when you start treatment ; 1- the cause 2- the severity 3- Age 4- Associated comorbid condition 5- presence of pregnancy

  20. According to the causes ; 1- congenital ; -Permanent ; Treatment with levothyroxine (L-T4) must be started immediately after the diagnosis of congenital hypothyroidism (CH early L-T4 treatment initiation (prior to 2 weeks of life) can prevent intellectual deficits and optimize neurodevelopmental outcomes. L-T4 alone is the treatment of choice. The initial dose depends upon the severity of CH. A higher initial L-T4 dose of 10 to 15 micrograms (ug)/kg/day (50 ug/day for full-term infants with severe CH) is recommended, especially for neonates with a very low pretreatment T4 level. A high initial L-T4 dose can normalize serum T4 in 3 days and TSH by two weeks of therapy.[19]  Duration The majority of full-term infants with severe CH require a short-term high dose L-T4 (50 ug per day) with dose reduction to 37.5 ug per day after TSH is normalized to avoid overtreating. L-T4 tablets crushed and mixed with a small amount (1 to 2 ml) of water or breast milk may be administered orally via a small spoon or syringe. L-T4 should be given at the same time each day and at a different time of the day from calcium, iron, and soy to avoid interference with the absorption of the drugs Follow up ; 1 to 2 weeks after the start of L-T4 therapy with follow-up TFT every two weeks until a complete normalization of TSH. Repeat TFT is recommended every 1 to 3 months until 1 year of age. Children should have follow-up visits with TFT obtained every 2 to 4 months between the ages of 1 to 3 years, and every 3-12 months until growth is completed. More frequent visits and laboratory evaluations may be scheduled for patients with poor adherence or abnormal levels. Any L-T4 dose adjustment or formulation change requires a repeat TFT in 4-6 weeks

  21. Duration Current guidelines recommend treatment with L-T4 until at least 36 months of age. At that time, a trial off of L-T4 can be considered to determine the permanency of congenital hypothyroidism. Transients ; L-T4 dose of less than 2.8 mcg/kg/day in the third year of treatment is a predictor of transient CH. Thus, early discontinuation of L-T4 therapy at 2.5 years of age may be possible with careful monitoring of TFT.[22] TFT should be repeated in 2 weeks after a trial time off the therapy. If repeat TFT is abnormal, L-T4 should be restarted. If repeat TFT is normal, TFT may be repeated again in 1 to 2 months to ensure normal thyroid hormone status

  22. Acquired ; - depends on severity and age 1- overt

  23. 3- in old age ;

  24. 4- at puberty ; Greater than 12 years but growth and puberty incomplete: 2 to 3 mcg/kg/day Growth and puberty complete: 1.6 mcg/kg/day 5- pregnancy ; Pregnant patients with newly diagnosed hypothyroidism should receive initial treatment at 1.8 mcg/kg/day. Adjust the dose every four weeks as needed. If a patient is diagnosed with hypothyroidism before pregnancy, adjust the dose of levothyroxine as needed. After pregnancy, levothyroxine should decrease to 1.6 mcg/kg/day.[17] The American Thyroid Association (ATA) recommends levothyroxine as the treatment of choice for maternal hypothyroidism. 6- Breast feeding ; The American Thyroid Association(ATA) suggests hypothyroidism should be treated with levothyroxine in lactating women. After delivery, levothyroxine should be reduced to the patient's preconception dose. Further thyroid function testing should be performed at approximately six weeks postpartum

  25. subclinical hypothyroidism ; - indication ; - if serum TSH level is more than 10 treat - if serum TSH level is 5-10 ; not to treat if ; - very old - negative TPO - No compiling indication indication for treatments ; - young - progressive increase - positive TPO - Compiling indication ; - S,S - Pregnancy , infertility , menstrual -CVD

  26. 7- Associated comorbid condition ; start low and go slow ; Patients at moderate or high risk - start with 12.5-25 ug Treatment target ;

  27. Algorithm for treatment

  28. treatment follow up ; 1- factors that effect levothyroxine dose ; There are many factors encountered by patients across their life span that may be associated with an altered levothyroxine requirement. Newborns, children, and adolescents typically require higher levothyroxine doses than adults [8]. Examples of factors affecting the levothyroxine dose requirements of adults include pregnancy, weight changes, hormonal changes, and ageing A - pregnancy ; factors lead to increase in the requirement ; - increase in thyroxine binding protein - placental volume The percentage increase in levothyroxine dose needed can be as high as 30–50% and is highest when the cause of the hypothyroidism is a thyroidectomy or ablation of the thyroid gland [35]. Achieving a serum TSH < 1.2 mIU/l preconception seems to reduce the percentage of patients requiring a dose increase [36]. Studies show that serum TSH can be maintained at goal during pregnancy by either increasing the levothyroxine dose by 29% by increasing from 7 to 9 tablets of levothyroxine weekly when conception is confirmed [37] or ongoing titration based on serum TSH [38]. The latter method had the advantage of resulting in fewer patients having a suppressed TSH during pregnancy [38]. Women undergoing in vitro fertilisation have similar needs for increased levothyroxine dosages, with 83% of women requiring an increase and the average increase being 33%

  29. B- Weight changes ; - weight based ; 1.6 ug/kg - TSH based ; LT4 dose =107+ ( 0.69 × TSH ) C- Hormonal changes ; , premenopausal women may require higher levothyroxine doses than postmenopausal women [40, 45, 46]. Conversely, oestrogen therapy is associated with a need for higher doses of levothyroxine to maintain the same serum TSH  D- Age ; Several studies have shown that the levothyroxine dose requirement is decreased in older individuals [8, 48, 49]. However, a recent study suggests that this decreased requirement may be mediated by the changes in weight that may accompany ageing [26]. Other important considerations regarding levothyroxine doses in older individuals include bearing age-adjusted TSH reference ranges in mind [50] and avoiding over-replacement that might potentially exacerbate other medical conditions [8]. Both of these considerations would lead to targeting of higher TSH values in older individuals

  30. E- Associated comorbid condition ; - thyroid cancer - CVD F- Dosage or drug quality issue E- Diet changes ; high fiber diet F- Medication ; iodine , estrogen G- Hashimoto's Disease Medical conditions can also lead you to have too much levothyroxine in your body. With Hashimoto's disease, your thyroid hormone levels can fluctuate rapidly. Hashitoxicosis occurs when your thyroid is over-functioning and producing more thyroid hormone.11 Taking your thyroid hormone replacement medication when your thyroid is in hashitoxicosis can temporarily cause symptoms of hyperthyroidism.11

  31. Monitoring •  adults, monitor TSH levels approximately 6 to 8 weeks after initiating treatment with levothyroxine. Upon achieving the correct dosing of levothyroxine, monitor TSH levels after 4 to 6 months and then every 12 months. Patients should receive education about the symptoms of hyperthyroidism and contact their clinician for medication dose decrease if those symptoms appear.[13][15] It is important to consider that TSH is unreliable in patients with secondary or tertiary hypothyroidism, and the best indicator to adjust dosing will be the free T4 or total T4.[27] The clinician should counsel the patient to use the same levothyroxine brand because of the narrow therapeutic index.[28] • Oral semaglutide (GLP-1 analog) increases total T4 exposure when given levothyroxine. In addition, levothyroxine pharmacokinetics is influenced by co-administration with oral semaglutide. Therefore, thyroid function tests should be monitored, and the clinician should adjust the levothyroxine dose

  32. Dose adjustement Aim ; in order to ovoid over or under treatment ; Factors that should be considered ; - - Age - the cause - body weight - duration and severity - associated comorbid condition

  33. Given the half-life of levothyroxine (approximately 1 week), reassessment of thyroid status by serum TSH levels, and free thyroxine levels if desired, is indicated after 6 weeks of therapy when the pharmacokinetic steady state is reached. If the TSH is not at the desired goal, the levothyroxine dose can be adjusted up or down. TSH values that are slightly out of range may be corrected by a single dose increment or decrement, such as increasing from 100 to 112 μg or decreasing from 175 to 150 μg. TSH values that are considerably out of range may require larger percentage changes. Levothyroxine absorption is maximised, at about 75% of the administered dose, when it is ingested upon an empty stomach [8]. Therefore, if levothyroxine is taken at other times of the day for convenience, the dose requirement may be greater and potentially more variable [15]. Once the desired TSH value has been achieved, it could potentially be re-confirmed by laboratory testing in 3–6 months, and then checked on an annual basis thereafter. A stable TSH while receiving levothyroxine therapy was inversely associated with the magnitude of the levothyroxine dose in one study, perhaps suggesting that residual thyroid function provided some buffer against TSH variations in those who required smaller levothyroxine doses

  34. After starting first dose ; check TSH level after 4-6 weeks ; - if the treatment target is reached continuous the same dose if the treatment target is not reached; types ; over or under treatment ( 48% )

  35. types • Undertreatment - diagnosis ; - clinical - laboratory Treatment ; increase the dose every 4-6 weeks according to ; 1 - Age ; Middle and young , increase by 50-75 ug Old age by 25-50ug Old age with CVD by 12.5 – 25 2 -Other high risk groups ( CVD , osteoporosis , ) by 12.5-25 3 - obese 4 - pregnancy ; increase the dose by 30%

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