Hypothyroidism management Prof. Ashraf Aminorroaya Isfahan Endocrine and Metabolism Research Center,Isfahan University of Medical Sciences Isfahan, Iran 21 April 2017

Case 1 (hypothyroidism management) A 35 years old woman with fatigue, muscle cramp, firm goiter (2*Nl), positive TPOAb and TSH=40 mIU/L. Questions: The best treatment Time of administration Intervals of follow up Target of treatment Duration of therapy

Case 2 (hypothyroidism management) A 75 years old man, known case of coronary artery disease and postablative hypothyroidism , with puffiness, dry hair and skin, constipation, TSH= 60 mIU/L. Questions: Dose of levothyroxine Intervals of follow up Target of treatment

Case 3 (hypothyroidism management) A 30 years old woman, known case of hypothyroidism and TSH> 100 mIu/L was treated for 12 weeks with 100 µg/d of levothyroxine. Now, she is, clinically, euthyroid. However, TSH level is still 35 mIu/L. Question: How do you treat the patient?

Case 4 (hypothyroidism management) A well-controlled hypothyroid patient for many years on a stable dose of levothyroxine, now, has symptoms and sign of hypothyroidism and TSH=30 mIu/L. Question: What could be the cause?

Central hypothyroidism known hypothalamic or pituitary disease A mass lesion is present in the pituitary When symptoms and signs of hypothyroidism are associated with other hormonal deficiencies

Treatment T4 : 1.6 mcg/kg /d, varying from 50 to ≥200 mcg/day Older patients should be started on a lower dose (25 to 50 mcg daily) Measure TSH after 6 weeks Young: 0.4 and 2.5 mU/L Old: age-adjusted upper limits of normal Goal: No symptoms with NL TSH and to avoid overtreatment (iatrogenic thyrotoxicosis), especially in the elderly THYROID Volume 24, Number 12, 2014 American Thyroid Association

Prescribing brand-name levothyroxine preparations? Yes Switches between levothyroxine products could potentially result in variations in the administered dose and should generally be avoided for that reason THYROID Volume 24, Number 12, 2014 American Thyroid Association

Time of levothyroxine administration Co-administration of food and levothyroxine impairs levothyroxine absorption 60 minutes before breakfast or at bedtime (3h or more after the evening meal) for optimal, consistent absorption THYROID Volume 24, Number 12, 2014 American Thyroid Association

Co-administration of medications and supplements with levothyroxine Avoid with potentially interfering medications and supplements (e.g., calcium carbonate and ferrous sulfate) A 4-hour separation is traditional, but untested. THYROID Volume 24, Number 12, 2014 American Thyroid Association

High dose levothyroxine requirement Investigate gastrointestinal conditions: Helicobacter pylori–related gastritis Atrophic gastritis Celiac disease THYROID Volume 24, Number 12, 2014 American Thyroid Association

Medications affect on T4 requirement by altered metabolism or binding to transport proteins Estrogen Androgens Phenobarbital Phenytoin Carbamazepine Rifampin Sertraline THYROID Volume 24, Number 12, 2014 American Thyroid Association

Factors determine the levothyroxine starting dose Patient’s weight Lean body mass Pregnancy status Etiology of hypothyroidism Degree of TSH elevation Age General clinical context, eg. cardiac disease THYROID Volume 24, Number 12, 2014 American Thyroid Association

Best approach to initiating and adjusting levothyroxine dosage Initial full replacement or Partial replacement with gradual increments in the dose titrated upward Using serum TSH as the goal Dose adjustments: Large changes in body weight Aging Pregnancy Assess TSH: 4–6 weeks after any dosage change. THYROID Volume 24, Number 12, 2014 American Thyroid Association

Potential deleterious effects of inadequate levothyroxine Detrimental effects on the serum lipid profile Progression of cardiovascular disease. THYROID Volume 24, Number 12, 2014 American Thyroid Association

Potential deleterious effects of excessive levothyroxine Atrial fibrillation Osteoporosis Avoid subnormal TSH, particularly below 0.1 mIU/L, especially in older persons and postmenopausal women. THYROID Volume 24, Number 12, 2014 American Thyroid Association

Management of hypothyroidism in elderly patients Initiate low dose and titrate slowly based on serum TSH Normal TSH range is higher in older populations (such as those over 65 years) Higher serum TSH target may be appropriate THYROID Volume 24, Number 12, 2014 American Thyroid Association

Management of hypothyroidism in pregnancy Dose titration to achieve TSH within the trimester specific reference range Check TSH every 4 weeks in the first half of pregnancy and less frequent later Increase T4 dosage as soon as pregnancy is confirmed THYROID Volume 24, Number 12, 2014 American Thyroid Association

Management of hypothyroidism in infants and children 10–15µg/kg/d T4 should be initiated once newborn screening is positive, pending the results of confirmatory testing Higher doses for infants with severe congenital hypothyroidism Goal: Serum thyroxine in the mid- to upper half of the pediatric and the serum TSH in the mid- to lower half of pediatric reference range Check T4 & TSH 2–4 weeks after initiation of therapy Once the proper dose is identified, surveillance testing should be performed every 1 to 2 months during the first year of life with decreasing frequency as the child ages. THYROID Volume 24, Number 12, 2014 American Thyroid Association

Biochemical treatment goal in secondary hypothyroidism Serum FT4 in the upper half of the reference range However, the serum free thyroxine target level may be reduced in older patients or patients with comorbidities, who may be at higher risk of complications of thyroid hormone excess THYROID Volume 24, Number 12, 2014 American Thyroid Association