thyroid health449 graves’ patients receiving mmi or ptu, 24% developed a cutaneous reaction 3.8%...

THYROID HEALTH

A REVIEW OF ATA GUIDELINES ON THYROID MANAGEMENT AND IMPLEMENTATION IN CLINICAL

PRACTICE

JAMES S CHOE MD

OBJECTIVES

Thyroid gland, Role of thyroid hormone, Thyroid regulation

Workup, etiology, and management of hyper and hypothyroidism in outpatient setting

DISCLAIMER

The opinions expressed in this presentation are strictly my own.

No relationship with the thyroid pharmaceutical industry

Will not apply to pediatric patients, pregnant patients, or hospitalized patients

JAMES CHOE

Oklahoma Native

Proud product of the Mid-Del school district

Attended Barnes Elementary and Carl Albert

Undergraduate at Yale University – studied History of Science/History of Med

Medical School, Internal Medicine Residency, Endocrinology Fellowship at OU

Recently moved to Choctaw area, enjoy gardening and fishing.

ENDOCRINOLOGY

Specializes in hormones of the human body

Diabetes mellitus

Adrenal dysfunction

Male reproductive hormones (testosterone)

Parathyroid hormone/calcium/osteoporosis

Pituitary dysfunction/tumors

Thyroid dysfunctions/tumors

CASE 1

One of your primary care patients is here for f/u after recent ER visit. 32 yo lady who developed

tremulousness, palpitations and was diagnosed with hyperthyroidism after recent ER visit. She was

started on atenolol. Labs show mild hyperthyroidism but improved from ER labs. She feels better.

She is getting back to work, getting better sleep (newborn is starting to sleep longer). Trace

tremulousness, mild tachycardia on exam – all better than before. Has appt with endocrinologist in 6

weeks. Overall she is improving, any specific questions to ask before end of visit?

CASE 2

81 yo man with recent normal labs except for TSH of 5.1 (0.5-4.5 normal). Free T4 1.1 (0.9-2.4

normal). Overall feels ok but has some fatigue. Should you start treatment? If so, how much.

CASE 3

55 yo lady new patient here to establish care. Was started on Armour thyroid after recent diagnosis

of hypothyroidism. She wants refill/continue Armour because she read that it is the more natural

option.

THYROID

U shaped or butterfly shaped gland in the neck

Typically 5 cm tall, 3 cm wide and 2 cm thick, average 10-20 grams

Requires iodine - obtained only by consumption

Recommended daily iodine intake adults, 150 mcg; pregnant women, 220 mcg; lactating women, 290

mcg.

-Food and Nutrition Council, National Academy of Medicine

-https://www.webmd.com/women/ss/slideshow-thyroid-symptoms-and-solutions

ROLE OF THYROID HORMONE

Affects function of cells in every system

Major targets are the heart, skeletal system, and metabolism

Influences bone growth, Increases heart rate, cardiac output, basal metabolic rate

Secreted by thyroid as pro hormone T4 (80%) and active T3 (20%)

80% of T3 arises from peripheral conversion from T4 by Deiodinase I and II

Pilo A, Iervasi G, Vitek F, Ferdeghini M, Cazzuola F, Bianchi R 1990 Thyroidal and peripheral production of 3,5,3′-triiodothyronine in humans by multicompartmental analysis. Am J Physiol

258:E715–726

More than 99.95 percent of the thyroxine (T4) and 99.5 percent of the triiodothyronine (T3) in serum

are bound to several serum proteins

Only the unbound “free” thyroid hormone is physiologically active,

Total T4 and Total T3 reflect both free and protein bound thyroid

not a good measure of active thyroid levels.

T3 T4

Protein

T3 T4

T

3

T

4

T3 T4

Protein

T3 T4

T3 T4

Protein

T3 T4

T3 T4

Protein

T3 T4

THYROID RELATED LABS

TSH

Total T4

Free T4

Total T3

Free T3

TBI/TBC

Thyroid binding index or thyroid binding capacity or T-uptake assay

Measure of the available thyroxine-binding sites.

FTI

Free Thyroidal Index

Thyroxine (T4)/Thyroid Binding Capacity

Estimated FT4

Antibodies

TPO

Thyroid peroxidase antibodies

Hashimotos

TSI/TRAB

Thyroid Stimulating Immunoglobulin/Thyroid receptor antibody

Graves

TG/TG antibodies

Thyroglobulin levels and thyroglobulin antibodies

Thyroid cancer

LOW VS HIGH THYROID

=

REGULATION OF THYROID

TSH is a reflection of how happy your brain is with the

amount thyroid hormone in your body

When TSH goes up – Brain is asking for more thyroid

hormone

Low Thyroid State

When TSH goes down – Brain is asking for less thyroid

hormone

High Thyroid State

HYPERTHYROIDISM - CAUSES

Medications

Grave’s Disease

Toxic Adenoma/Toxic Multinodular Goiter

Thyroiditis

Postpartum thyroiditis

Subacute thyroiditis

HYPERTHYROIDISM

Severity? Hemodynamically stable?

BP? Afib?

History

Duration? Meds? Recent pregnancy? Recent illness?

Exam

Tremulousness? Goiter? Neck Tenderness?

W/U

TSH, FT4, TSI

Uptake scan


Medications

Grave’s Disease


Thyroiditis



Long term problem

Short term problem

MEDICATIONS

Ross, Douglas S., et al. “2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis.” Thyroid, vol. 26, no. 10,

2016, pp. 1343–1421., doi:10.1089/thy.2016.0229.

GRAVES’ DISEASE

Classic symptoms include

weight loss

heat intolerance

Tremor

palpitations/afib

Anxiety

increased frequency of bowel movements

shortness of breath

Davies, T. Pathogenesis of Graves’ disease In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019.

May also have

goiter,

eye disease (opthalmopathy)

dermopathy referred to as pretibial or localized myxedema.

Driven by TSH receptor antibodies (TRAB) that stimulate thyroid

production

TRAB/TSI

Autoantibodies to the TSH receptor

Stimulates thyroid hormone synthesis and secretion

Sensitivity and specificity of 97 and 99 percent for diagnosing Graves' disease

Estimated that the use of TRAb over RAIU reduce costs by 47% and result in a 46% quicker diagnosis

When TRAb measurement is negative,

Consider radioiodine uptake vs thyroid blood flow by ultrasonography

Barbesino, Giuseppe, and Yaron Tomer. “Clinical Utility of TSH Receptor Antibodies.” The Journal of Clinical Endocrinology & Metabolism, vol. 98, no. 6, 2013, pp. 2247–2255.,

doi:10.1210/jc.2012-4309.

RADIOACTIVE UPTAKE

Pt ingests radioactive iodine capsule. After 24 hours, a gamma probe is placed over the thyroid gland

in the neck to measure the amount of radioactivity in the thyroid gland

Reported as percentage compared to dose given

Uptake elevated in patients with GD and normal or high in toxic nodular goiter

Near zero in thyroiditis (painless, postpartum, or subacute)

Toxic adenoma’s show focal uptake in the adenoma with suppressed uptake in the surrounding and

contralateral thyroid tissue.

RADIOACTIVE UPTAKE

Pregnancy and breastfeeding are absolute contraindications to radionucleotide imaging

Not accurate if pt had recent exposure to high dose of iodine (radiocontrast or kelp)

GRAVES’ DISEASE PRETIBIAL MYXEDEMA

Shins

raised, hyperpigmented, violaceous, orange-peel-textured papules

deposition of hyaluronic acid in the dermis and subcutis stimulated by TRAB

Primarily cosmetic issue

Warrants dermatology evaluation

Local application of corticosteroids remains the mainstay of treatment.

Ross, D. Overview of the clinical manifestations of hyperthyroidism in adultsIn: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019.

GRAVES’ DISEASE PRETIBIAL MYXEDEMA

https://synapse.koreamed.org/search.php?where=aview&id=10.5021/ad.2018.30.5.592&code=0140AD&vmode=PUBREADER

https://pmj.bmj.com/content/94/1110/236

http://img.medscape.com/pi/iphone/medscapeapp/html/A1103765-business.html

https://synapse.koreamed.org/search.php?where=aview&id=10.5021/ad.2018.30.5.592&code=0140AD&vmode=PUBREADER

GRAVES’ EYE DISEASE

Inflammation of the extraocular muscles and orbital fat and connective tissue

Proptosis (exophthalmos),

Impairment of eye muscle function

Periorbital and conjunctival edema

More common in patients who smoke cigarettes.

Treatment

Mild to mod severity – supportive, +/- steroids

Medical emergency (Loss of color vision)

Hospitalization and IV steroids

https://www.sciencephoto.com/media/862200/view/graves-ophthalmopathy

Ross, D. Treatment of Graves' orbitopathy (ophthalmopathy): UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019.

THYROID STORM

Rare, life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis

Cardiac

Tachycardia, CHF, hypotension, arrhythmia,

Fever

Neuropsychiatric

Considered by many to be essential to the diagnosis.

Agitation, anxiety, delirium, psychosis, stupor, or coma

Other symptoms may include severe nausea, vomiting, diarrhea, abdominal pain, or hepatic failure with jaundice.

Thyroid labs typically not any worse than uncomplicated hyperthyroidism

Ross, D. Thyroid StormUpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019.

THYROID STORM

While this scoring

system is likely

sensitive, it is not very

specific.

Degree of

hyperthyroidism is not

a criterion for

diagnosing thyroid

storm

Ross, Douglas S., et al. “2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis.” Thyroid, vol.

26, no. 10, 2016, pp. 1343–1421., doi:10.1089/thy.2016.0229.

THYROID STORM MANAGEMENT

ICU admission

PTU > Methimazole

Blocks T4-to-T3 conversion

T3 levels drop by approximately 45 percent within 24 hours after PTU

10 to 15 percent within 24 hours after methimazole


26, no. 10, 2016, pp. 1343–1421., doi:10.1089/thy.2016.0229.


26, no. 10, 2016, pp. 1343–1421., doi:10.1089/thy.2016.0229.

THYROID STORM

Iodine therapy should be administered at least 1 hour AFTER thionamides to prevent stimulation of

new thyroid hormone synthesis

Avoid aspirin because it displaces T4 from thyroid binding globulin, resulting in increase of free T4.

Titrate beta blockers carefully as excessive doses in thyrotoxic patients can cause cardiovascular

collapse.

Besides reducing T4 to T3 conversion, steroids provide adrenal support, which can be impaired in

thyroid storm.


26, no. 10, 2016, pp. 1343–1421., doi:10.1089/thy.2016.0229.

GRAVES’ DISEASE MANAGEMENT

Methimazole first line

Except first trimester of pregnancy, treatment of thyroid storm, reaction to MMI

PTU preferred

In a recent systematic review of eight studies that included 667 GD patients receiving

MMI or PTU, 13% of patients experienced adverse events.

Hepatocellular injury

2.7% of patients taking PTU and 0.4% of patients taking MMI.

Prummel MF, Wiersinga WM, Mourits MP, Koornneef L, Berghout A, van der Gaag R 1990 Effect of abnormal thyroid function on the severity of Graves'

ophthalmopathy. Arch Intern Med 150:1098–1101.

Ross, Douglas S., et al. “2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of

Thyrotoxicosis.” Thyroid, vol. 26, no. 10, 2016, pp. 1343–1421., doi:10.1089/thy.2016.0229.


449 Graves’ patients receiving MMI or PTU,

24% developed a cutaneous reaction

3.8% developed transaminase elevations more than 3-fold above normal

0.7% developed agranulocytosis (absolute neutrophil count <500)

Andersohn F, Konzen C, Garbe E 2007 Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med 146:657–665

Otsuka F, Noh JY, Chino T, Shimizu T, Mukasa K, Ito K, Ito K, Taniyama M 2012 Hepatotoxicity and cutaneous reactions after antithyroid drug administration. Clin

Endocrinol (Oxf) 77:310–315.

AGRANULOCYTOSIS

Agranulocytosis - Sudden drop in WBC, neutrophil count <500

Clinically present with sudden fever and sore throat

Uncommon but life-threatening.

PTU at any dose appears to be more likely to cause agranulocytosis than low doses of MMI

Can occur quickly. Even if CBC was recently before, patients need to seek urgent

medical attention for new sudden fever and sore throat

Before starting ATDs and at each subsequent visit, the patient should be alerted to stop

the medication immediately and call their physician if there are symptoms suggestive of

agranulocytosis or hepatic injury.

Andersohn F, Konzen C, Garbe E 2007 Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med 146:657–665

Otsuka F, Noh JY, Chino T, Shimizu T, Mukasa K, Ito K, Ito K, Taniyama M 2012 Hepatotoxicity and cutaneous reactions after antithyroid drug administration. Clin

Endocrinol (Oxf) 77:310–315.

CHOICE OF BETA BLOCKER




Smoking is the most important known risk factor for the development or worsening of Graves eye

complications

Both firsthand and secondhand smoking increase eye complication risk






Reassess serum free T4 and total T3 approx. 2–6 weeks after initiation of therapy

Serum T3 should be monitored because the serum free T4 levels may normalize despite persistent

elevation of serum total T3.

TSH may remain suppressed for several months after starting therapy,

Not a good parameter for monitoring therapy early in the course.






Once efforts made to achieve euthyroidal state, consider long term management options

Continue antithyroidals

Radioactive ablation

Surgery


RAI therapy:

Women planning a pregnancy (more than 6 months away)

Increased surgical risk

contraindications to ATD use or failure to achieve euthyroidism during treatment with ATDs.

ATDs:

High likelihood of remission (mild disease, small goiters, and negative or low-titer TRAb)

Pregnancy

The elderly or high surgical risk

Surgery:

Women planning a pregnancy in <6 months

Symptomatic compression or large goiters

When thyroid malignancy is documented or suspected (e.g., suspicious or indeterminate cytology);

Coexisting hyperparathyroidism requiring surgery

Patients with moderate to severe active GO.




Medications

Grave’s Disease


Thyroiditis



POST PARTUM THYROIDITIS

Triphasic pattern is hyper->hypo->normal

Hyperthyroid at 1–6 months postpartum

Hypothyroidism and return to euthyroidism at 9–12 months postpartum

Treat with beta blockers

Roti E, Uberti E 2002 Post-partum thyroiditis—a clinical update. Eur J Endocrinol 146:275–279.

Davanzo R, Rubert L, Oretti C 2008 Meta-variability of advice on drugs in the breastfeeding mother: the example of beta-blockers.Arch Dis Child Fetal Neonatal Ed 93:F249–50.

POST PARTUM THYROIDITIS – BETA BLOCKERS

Use propranolol or metoprolol. Do not use atenolol

Propranalol and metoprolol are secreted into breast milk in only very low amounts

Atenolol should not be used in breastfeeding mothers because it may lead to symptoms consistent

with β-adrenergic blockage in neonates.

Roti E, Uberti E 2002 Post-partum thyroiditis—a clinical update. Eur J Endocrinol 146:275–279.

Davanzo R, Rubert L, Oretti C 2008 Meta-variability of advice on drugs in the breastfeeding mother: the example of beta-blockers.Arch Dis Child Fetal Neonatal Ed 93:F249–50.

CASE 1

One of your primary care patients is here for f/u after recent ER visit. 32 yo lady who developed

tremulousness, palpitations and was diagnosed with hyperthyroidism after recent ER visit. She was

started on atenolol. Labs show mild hyperthyroidism but improved from ER labs. She feels better.

She is getting back to work, getting better sleep (newborn is starting to sleep longer). Trace

tremulousness, mild tachycardia on exam – all better than before. Has appt with endocrinologist in 6

weeks. Overall she is improving, any specific questions to ask before end of visit?

CASE 1

Ask if she is breastfeeding.

SUBACUTE THYROIDITIS

Hyperthyroidism with painful neck 6-8 weeks after viral infection.

Thought to be viral infection or post infection thyroid inflammation resulting in release of stored

thyroid hormone

Diagnosis

+ESR/CRP

RAIU low

US doppler decreased flow or normal flow

SUBACUTE THYROIDITIS

The thyrotoxic phase usually lasts 3–6 weeks,

30% become hypothyroid

Lasts up to 6 months.

Thyroid pain and the elevated ESR have usually resolved by this time, and the predominant clinical features are

those of hypothyroidism with a small nontender goiter.

85-95% recover by 12 months

Can have persistent hypothyroidism

In addition, recurrence rates of 1%–4% have been reported

Fatourechi V, Aniszewski JP, Fatourechi GZ, Atkinson EJ, Jacobsen SJ 2003 Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota,

study. J Clin E ndocrinol Metab88:2100–2105.

SUBACUTE THYROIDITIS TREATMENT

Treat with beta blockers and NSAIDS as first-line therapy

Median time for resolution of pain is 5 weeks (range 1–20 weeks)

Should improve over a few days

Corticosteroids when patients fail to respond or have moderate to severe pain and/or thyrotoxic

symptoms.

Fatourechi V, Aniszewski JP, Fatourechi GZ, Atkinson EJ, Jacobsen SJ 2003 Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted County, Minnesota, study. J

Clin Endocrinol Metab88:2100–2105.

OTHER THYROIDITIS

Painless thyroiditis

Similar to subacute but no thyroid pain

Acute thyroiditis

Suppurative thyroiditis or thyroid abscess

Palpation thyroiditis

Palpation of the thyroid gland at surgery

HYPERTHYROIDISM – UNUSUAL CAUSES

Struma Ovarii

Teratoma predominantly composed of mature thyroid tissue

Choriocarcinoma

tumor-derived hCG stimulating TSH receptor

TSH secreting pituitary tumor

Factitious

SUMMARY

Assess severity

Hemodynamics/vitals

TSH, FT4, Total T3

ER vs Endocrinology

Determine etiology

GD, TA/TMNG - TRAB/TSI, uptake scan, US

Thyroiditis - Postpartum? Thyroid pain? Meds?

Treat or observe

Beta blockers, methimazole, +/- steroids

Refer to endocrinologist early

How many psychiatrists does it take to change a lightbulb?

Only one; but it really has to want to change.

HYPOTHYROIDISM

Hypothyroidism is 5x-8x more common in women than men,

More common in women with small body size at birth and during childhood

Most common etiology in US - chronic autoimmune thyroiditis (Hashimoto's thyroiditis).

Most common sx

Dry skin, cold sensitivity, fatigue, muscle cramps, and constipation

Aoki, Yutaka, et al. “Serum TSH and Total T4 in the United States Population and Their Association With Participant Characteristics: National Health and Nutrition Examination Survey (NHANES 1999–2002).” Thyroid, vol. 17,

no. 12, 2007, pp. 1211–1223., doi:10.1089/thy.2006.0235.

HYPOTHYROIDISM TYPES

Primary

Problem with thyroid

Secondary

Pituitary issue

• Published in 2014

• “Review the goals of levothyroxine therapy, the optimal prescription of conventional

levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence

on treatment alternatives, and the relevant knowledge gaps.”

• Identified 24 questions relevant to the treatment of hypothyroidism and reviewed clinical

literature

• Clinical recommendations were graded according to the ACP grading system for evidence and

recommendations

SCREENING

Jonklaas, Jacqueline, et al. “Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement.” Thyroid, vol. 24, no. 12, 2014,

pp. 1670–1751., doi:10.1089/thy.2014.0028.

SCREENING

In addition

Autoimmune disease(DMI), first-degree relative with autoimmune thyroid disease

Pernicious anemia

History of neck radiation to the thyroid gland

Radioactive iodine therapy for hyperthyroidism and external beam radiotherapy for head and neck malignancies

Prior history of thyroid surgery or dysfunction

Those with psychiatric disorders

Patients taking amiodarone or lithium


pp. 1670–1751., doi:10.1089/thy.2014.0028.


pp. 1670–1751., doi:10.1089/thy.2014.0028.

Z13.29 (ICD 10)

Encounter for screening for other suspected endocrine disorder.

DIAGNOSIS

Primary

Over 95 percent of cases of hypothyroidism.

TSH above normal with symptoms of hypothyroidism

Typically Hashimotos

Subclinical Hypothyroid – TSH high but no symptoms and FT4 and total T3 normal


pp. 1670–1751., doi:10.1089/thy.2014.0028.

HYPOTHYROIDISM TYPES

Secondary and tertiary hypothyroidism should be suspected in the following circumstances:

There is 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

Ross, D. Diagnosis of and screening for hypothyroidism in nonpregnant adultsIn: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019.

WHEN TO REFER TO ENDOCRINOLOGIST

Children and infants

Patients in whom it is difficult to render and maintain a euthyroid state

Pregnancy

Women planning conception

Cardiac disease

Presence of goiter, nodule, or other structural changes in the thyroid gland

Presence of other endocrine disease such as adrenal and pituitary disorders

Unusual constellation of thyroid function test results

Unusual causes of hypothyroidism such as those medication induced

Anytime you feel that it is appropriate!


pp. 1670–1751., doi:10.1089/thy.2014.0028.

TPO ANTIBODIES

Antibodies to thyroid peroxidase enzyme in thyroid gland related production of thyroid hormones

No need to routinely measure TPO antibodies in patients with primary overt hypothyroidism

Almost all primary hypothyroid patients have chronic autoimmune thyroiditis.

Serum concentrations of TPO autoantibodies are elevated in more than 90 percent of patients

The presence of elevated TPOAb titers in patients with subclinical hypothyroidism helps to predict

progression to overt hypothyroidism

4.3% per year with + TPO antibodies

If + TPO Ab, measure serum TSH annually.

Mariotti, S., et al. “Antithyroid Peroxidase Autoantibodies in Thyroid Diseases*.” The Journal of Clinical Endocrinology & Metabolism, vol. 71, no. 3, 1990, pp. 661–669., doi:10.1210/jcem-71-3-661.

TG AND TG ANTIBODIES

Thyroglobulin

Protein produced by normal thyroid cells (also thyroid cancer cells)

It is not a measure of thyroid function

Will be present if thyroid gland is present

The presence of thyroglobulin antibodies indicates lab testing for thyroglobulin levels are not accurate

It is used most often in patients who have had surgery for thyroid cancer in order to monitor them

after treatment.

Thyroid Function Tests from thyroid.org. https://www.thyroid.org/thyroid-function-tests/.

THYROID REPLACEMENT

Until the 1970s, desiccated thyroid extracts was main form of thyroid replacement.

The paradigm began to shift

After the synthesis of T4

Demonstration that the biologically active T3 was generated from T4 in humans

Braverman LE, Ingbar SH, Sterling K 1970 Conversion of thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects. J Clin Invest 49:855–864.

LEVOTHYROXINE

Levothyroxine/T4

Synthesized form of natural human hormone

Prohormone with little intrinsic activity.

Deiodinated in peripheral tissues to form T3

This deiodination process accounts for approximately 80 percent of the total daily production of T3 in normal subjects.

Approximately 70 to 80 percent of a dose of T4 is absorbed

Half-life of T4 is ~ 7 days,

Steady-state levels of T4 and TSH are generally achieved in 6 weeks (approximately five to six half-lives) after initiation of therapy

Fish LH, Schwartz HL, Cavanaugh J, Steffes MW, Bantle JP, Oppenheimer JH 1987 Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. Role

of triiodothyronine in pituitary feedback in humans. N Engl J Med 316:764–770.

Ross, D. Treatment of primary hypothyroidism in adults, Post, TW (Ed), UpToDate, Waltham, MA, 2019

GOAL OF REPLACEMENT

Clinical and biochemical goals for levothyroxine replacement per ATA

Provide resolution of the patients' symptoms and hypothyroid signs, including biological and physiologic

markers of hypothyroidism

Achieve normalization of serum thyrotropin with improvement in thyroid hormone concentrations

Avoid overtreatment (iatrogenic thyrotoxicosis), especially in the elderly


pp. 1670–1751., doi:10.1089/thy.2014.0028.

GOAL OF REPLACEMENT

Symptoms alone may not be reliable in adjusting thyroid doses

A randomized controlled trial published in JCEM took 56 subjects with primary hypothyroidism and gavethree T4 doses (low, middle, and high in 25mcg increments) in random order.

Assessed visual analog scales assessing well-being and hypothyroid symptoms, quality of life instruments (General Health Questionnaire 28, Short Form 36, and Thyroid Symptom Questionnaire), cognitive function tests, and treatment preference.

Demonstrated that patients are unable to detect differences in the symptoms associated with hypothyroidism when the LT4 dose is changed by approximately 20%.

Change in dosage was sufficient to modify cholesterol levels

Walsh JP, Ward LC, Burke V, Bhagat CI, Shiels L, Henley D, Gillett MJ, Gilbert R, Tanner M, Stuckey BG 2006 Small changes in thyroxine dosage do not produce measurable changes

in hypothyroid symptoms, well-being, or quality of life: results of a double-blind, randomized clinical trial. J Clin Endocrinol Metab91:2624–2630.

STARTING DOSE

Estimate of required thyroid hormone typically1.6–1.8 μg/kg of actual body weight

The etiology of a patient's hypothyroidism affects their LT4 dose

Depends on amount of residual thyroid function

Total thyroidectomy patients generally require a higher LT4 dose than patients with Hashimoto's thyroiditis.

Fish LH, Schwartz HL, Cavanaugh J, Steffes MW, Bantle JP, Oppenheimer JH 1987 Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of

hypothyroidism. Role of triiodothyronine in pituitary feedback in humans. N Engl J Med 316:764–770.

Burmeister LA, Goumaz MO, Mariash CN, Oppenheimer JH 1992 Levothyroxine dose requirements for thyrotropin suppression in the treatment of differentiated thyroid

cancer. J Clin Endocrinol Metab75:344–350.

STARTING DOSE

The full calculated daily LT4 dose may be given initially to young and middle-aged patients who are otherwise healthy,

“Start low and go slow” for elderly patients and those with cardiovascular disease

Consider starting at 25mcg and increase in 25mcg increments based on symptoms and serum TSH levels.

Can precipitate cardiac events.

However, one randomized trial showed that even elderly hypothyroid patients who are free of cardiovascular disease, as assessed by a dobutamine stress echocardiogram and bicycle ergometry at 12 and 24 weeks, may be safely started on the full replacement dose.

Thyroid functional parameters improved more rapidly in patients given the full dose rather than lower doses.

Roos A, Linn-Rasker SP, van Domburg RT, Tijssen JP, Berghout A 2005 The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind

trial. Arch Intern Med165:1714–1720.

STARTING DOSE

ATA Recommendation

Thyroid hormone therapy should be initiated as an initial full replacement or as partial replacement with

gradual increments in the dose titrated upward using serum thyrotropin as the goal. Dose adjustments should

be made when there are large changes in body weight, with aging, and with pregnancy, with thyrotropin

assessment 4–6 weeks after any dosage change.

Strong recommendation. Moderate quality of evidence.


pp. 1670–1751., doi:10.1089/thy.2014.0028.

ADJUSTMENTS FOR ELDERLY

Typically need lower doses due to changes in T4 metabolism

TSH levels rise with age in normal individuals

97.5% confidence interval for serum TSH in healthy elderly persons is 7.5 mIU/L

There are observational data showing decreased mortality rates and improved measures of well-being in elderly persons with TSH levels that are above the traditional reference range (i.e., 0.5–4.5 mIU/L).

Also observational data showing that higher FT4 concentrations are associated with mortality in the elderly

-Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, Bacharach P, Wilson PW, Benjamin EJ, D'Agostino RB1994 Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl

J Med 331:1249–1252. Crossref, Medline, Google Scholar

-Bauer DC, Ettinger B, Nevitt MC, Stone KL 2001 Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med 134:561–568. Crossref, Medline, Google Scholar

-Surks MI, Hollowell JG 2007 Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol

Metab92:4575–4582. Crossref, Medline, Google Scholar

-Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG 2004 Thyroid status, disability and cognitive function, and survival in old age. JAMA292:2591–2599. Crossref, Medline, Google

Scholar

-Waring AC, Arnold AM, Newman AB, Buzkova P, Hirsch C, Cappola AR 2012 Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. J Clin

Endocrinol Metab 97:3944–3950. Crossref, Medline, Google Scholar


Normal TSH 0.3 - 4.8 mIU/L

Normal FT4 1.01 - 1.79 ng/dL

23% decrease in mortality risk for

2.71mIU/L increase in TSH

16% increase in mortality risk for

0.21ng/dL increase in FT4.

-Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frolich M, Westendorp RG 2004 Thyroid status, disability and cognitive function, and survival in old age. JAMA292:2591–2599. Crossref, Medline, Google

Scholar

OVER REPLACEMENT

Patients older than age 65 with serum TSH levels <0.1 mIU/L had 3x increase in the risk of atrial

fibrillation over a 10-year observation period compared to euthyroid controls

The risk for low bone density and fractures is also elevated in postmenopausal (but not

premenopausal) women taking LT4 and low TSH.

ATA Recommendation:

Avoid thyroid hormone excess and subnormal serum thyrotropin values, particularly thyrotropin values below

0.1 mIU/L, especially in older persons and postmenopausal women.

Strong recommendation. Moderate quality evidence.

-Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, Bacharach P, Wilson PW, Benjamin EJ, D'Agostino RB1994 Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older

persons. N Engl J Med 331:1249–1252. Crossref, Medline, Google Scholar

-Bauer DC, Ettinger B, Nevitt MC, Stone KL 2001 Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med 134:561–568. Crossref, Medline, Google Scholar

-Flynn RW, Bonellie SR, Jung RT, MacDonald TM, Morris AD, Leese GP 2010 Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on

long-term thyroxine therapy. J Clin Endocrinol Metab 95:186–193. Crossref, Medline, Google Scholar

CASE 2

81 yo man with recent normal labs except for TSH of 5.1 (0.5-4.5 normal). Free T4 1.1 (0.9-2.4

normal). Overall feels ok but has some fatigue. Should you start treatment? If so, how much.


Based on the current evidence it is reasonable to raise the target serum TSH to 4–6 mIU/L in persons

greater than age 70–80 years.


pp. 1670–1751., doi:10.1089/thy.2014.0028.

Canaris GJ, Manowitz NR, Mayor G, Ridgway EC 2000The Colorado thyroid disease prevalence study. Arch Intern Med 160:526–534.

ADJUSTMENTS FOR PREGNANCY

Changes in pregnancy

An increase in serum thyroxine-binding globulin (TBG)

Stimulation of the thyrotropin receptor by human chorionic gonadotropin (hCG)

Immediately start 30% increase at time of pregnancy,

Extra dose 2x week

Monitor levels every 4 weeks (for 1st half of pregnancy) and adjust dose to trimester specific ranges


pp. 1670–1751., doi:10.1089/thy.2014.0028.

Ross, D. Overview of thyroid disease and pregnancy UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019

BRAND VS GENERIC

Brand nam e vs generic? S hould you switch between thyroid m eds?

ATA Recommendation

Switches between levothyroxine products could potentially result in variations in the administered dose and

should generally be avoided for that reason (see also recommendation 3d).

Weak recommendation. Low-quality evidence (for general populations)

Strong recommendation. Low-quality evidence (frail patients, high-risk thyroid cancer patients, pregnant

patients)

Strong recommendation. Moderate-quality evidence (early childhood hypothyroidism)


pp. 1670–1751., doi:10.1089/thy.2014.0028.

BRAND VS GENERIC

Since 2007 the FDA has required that LT4 preparations maintain 95%–105% of their stated potency, revised from a prior requirement of 90%–110%, throughout their shelf life

Also required that all LT4 products be reassessed as though they were new drugs

When a generic or branded LT4 preparation meets the criteria noted above for bioequivalence and potency, the FDA has determined that LT4 preparations can be substituted for one another by the pharmacy, unless specifically designated to be dispensed as written by the prescriber.

ATA, Endocrine Society, and American Association of Clinical Endocrinologists recommend repeat thyroid function testing when a patient is switched from one LT4 preparation to another to ensure the goal TSH (and FT4 and T3) concentrations are achieved

•U.S. Food and Drug Administration. FDA acts to ensure thyroid drugs don't lose potency before expiration date.

•U.S. Food and Drug Administration. Questions and answers on levothyroxine sodium products.

•U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for Industry: Levothyroxine sodium products, enforcement of August 14,

2001, compliance date and submission of new applications.

•American Association of Clinical Endocrinologists, the Endocrine Society, and the American Thyroid Association Joint Position Statement on the Use and Interchangeability of Thyroxine Products, 2004.

METHOD OF TAKING

Gastrointestinal absorption of the tablet formulation of LT4 is in the 70%–80% range in healthy fasting

adults

Transient peak in serum T4 and free FT4 levels of about 15% magnitude about 4 hours after dose

Fiber and soy products appear to be associated with impaired LT4 absorption (case studies)

Increased TSH values seen in patients combining LT4 with espresso coffee (case studies)

Absorption studies performed in these patients and in volunteers support the role of coffee in reducing LT4

absorption.

-Hays MT, Nielsen KR 1994 Human thyroxine absorption: age effects and methodological analyses. Thyroid4:55–64.

-Saberi M, Utiger RD 1974 Serum thyroid hormone and thyrotropin concentrations during thyroxine and triiodothyronine therapy. J Clin Endocrinol Metab39:923–927.

-Ain KB, Pucino F, Shiver TM, Banks SM 1993 Thyroid hormone levels affected by time of blood sampling in thyroxine-treated patients. Thyroid 3:81–85.

-Liel Y, Harman-Boehm I, Shany S 1996 Evidence for a clinically important adverse effect of fiber-enriched diet on the bioavailability of levothyroxine in adult hypothyroid patients. J Clin Endocrinol Metab 81:857–859.

-Bell DS, Ovalle F 2001 Use of soy protein supplement and resultant need for increased dose of levothyroxine. Endocr Pract 7:193–194.

-Benvenga S, Bartolone L, Pappalardo MA, Russo A, Lapa D, Giorgianni G, Saraceno G, Trimarchi F 2008 Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid 18:293–301.

METHOD OF TAKING

ATA Recommendation

Where feasible, levothyroxine should be separated from other potentially interfering medications and

supplements (e.g., calcium carbonate and ferrous sulfate). A 4-hour separation is traditional, but untested.

Other medications (e.g., aluminum hydroxide and sucralfate) may have similar effects, but have been

insufficiently studied.

Weak recommendation. Weak quality evidence.


pp. 1670–1751., doi:10.1089/thy.2014.0028.

TIMING OF DOSE

In one study, patients took dose1 hour before breakfast, with breakfast, or at bedtime for 8 weeks.

The mean TSH values seen with these different conditions were 1.06, 2.93, and 2.19 mIU/L respectively

In the other study, (double-blind design), patients took either LT4 or placebo capsules 30 minutes

before breakfast and at bedtime for 12 weeks of each regimen.

105 in Netherlands

TSH values were 0.9–1.6 mIU/L higher with the morning compared with the bedtime LT4 ingestion

Only 30 mins before breakfast vs several hours after last meal at bedtime

Fasting is key

Bach-Huynh TG, Nayak B, Loh J, Soldin S, Jonklaas J2009 Timing of levothyroxine administration affects serum thyrotropin concentration. J Clin Endocrinol Metab 94:3905–3912.

Bolk N, Visser TJ, Nijman J, Jongste IJ, Tijssen JG, Berghout A 2010 Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Arch Intern Med 170:1996–

2003.

METHOD OF TAKING

ATA Recommendation

Because co-administration of food and levothyroxine is likely to impair levothyroxine absorption, we recommend

that, if possible, levothyroxine be consistently taken either 60 minutes before breakfast or at bedtime (3 or

more hours after the evening meal) for optimal, consistent absorption.

Weak recommendation. Moderate quality of evidence.


pp. 1670–1751., doi:10.1089/thy.2014.0028.

TIMING OF DOSE

Optimal time for LT4 absorption is important

But equally as important is considering timing that promotes adherence.

For example, although a fasting regimen may promote absorption, it may have the disadvantage of being maximally inconvenient for patients.

Consider patient's schedule and preference

If dose LT4 1 hour before breakfast is not feasible, a bedtime regimen may be the next best choice.

Another regimen that is consistently maintained, such as 30 minutes before breakfast, may also be reasonable.

Consume a breakfast with similar daily food choices and avoid foods that are most noted for interfering with LT4 absorption.


pp. 1670–1751., doi:10.1089/thy.2014.0028.

DOSE TITRATION

ATA Recommendation on persistant symptoms despite normalization of TSH

A minority of patients with hypothyroidism, but normal serum thyrotropin values, may perceive a suboptimal

health status of unclear etiology. Acknowledgment of the patients' symptoms and evaluation for alternative

causes is recommended in such cases. Future research into whether there are specific subgroups of the

population being treated for hypothyroidism who might benefit from combination therapy should be

encouraged.

Weak recommendation. Low-quality evidence.

CAN WE RELY ON TSH?

1st generation tests had detection limits of approximately 1 mU/L

3rd generation tests (current) are now down to 0.01mU/L

TSH normal ranges

Adults 21-54 years: 0.4-4.2

55-87 years: 0.5-8.9

National Health and Nutrition Examination Survey III sampled16,000 people

97.5 % of people in the 20–29 year old were less than 3.56 mIU/liter and 80+ year old were less than 7.49 mIU/liter

Surks MI , Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin

Endocrinol Metab . 2007;92:4575–4582

CAN WE RELY ON TSH?

Heterophilic antibodies can cause high TSH

Repeating the TSH in another assay, measurement of TSH in serial dilution, or direct measurement of human

anti-mouse antibodies.

High doses of biotin may cause low TSH as well as high FT4

Patients taking high doses of biotin or supplements containing biotin, who have elevated T4 and suppressed

TSH, should stop taking biotin and have repeat measurements at least 2 days later.

Surks MI , Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin

Endocrinol Metab . 2007;92:4575–4582

MONITORING T3

ATA summary statement

The significance of perturbations in serum triiodothyronine concentrations within the reference range or of

mildly low serum triiodothyronine concentrations is unknown.

Patients with hypothyroidism treated with levothyroxine to achieve normal serum TSH values may have serum

triiodothyronine concentrations that are at the lower end of the reference range, or even below the reference

range. The clinical significance of this is unknown.

RT3 AND NONTHYROIDAL ILLNESS

rT3 is the product of 5-monodeiodination of T4 (D3)

Elevated when critically ill

Nonthyroidal illness, especially in the setting of hypoxia or

ischemia increases D3

In addition, 5'-monodeiodinase is inhibited leading to

decreased rT3 clearance

Results in suppressed TSH, low FT4 and T3 and elevated

rT3

Ross, D. Thyroid function in nonthyroidal illness. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019.

ROLE OF RT3

rT3 is best used in critically ill/hospitalized pt with low TSH and low FT4 to distinguish between

central hypothyroidism and nonthyroidal illness.

Euthyroid patients with nonthyroidal illness may have transient elevations in serum TSH

concentrations (up to 20 mU/L) during recovery from nonthyroidal illness.

In patients with a recent illness, TSH and free T4 should be repeated four to six weeks after recovery.

Few of these patients prove to have hypothyroidism when reevaluated after recovery from their

illness.

Ross, D. Diagnosis of and screening for hypothyroidism in nonpregnant adultsIn: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019.

EUTHYROID TREATMENT

ATA 10a. Is there a role for the use of levothyroxine to treat biochemically euthyroid patients with

symptoms that overlap with those of hypothyroidism?

ATA 10c. Is there a role for the use of levothyroxine to treat euthyroid patients with obesity?

EUTHYROID TREATMENT

In a randomized placebo controlled cross-over trial in patients with symptoms suggestive of

hypothyroidism but biochemical euthyroidism, LT4 was no more effective than placebo in improving

cognitive and psychological well-being scores despite increases in serum FT4 and decreases in serum

TSH when study subjects were receiving LT4.

A study employing 12 months of TSH suppression therapy in euthyroid patients with thyroid nodules

did not detect any changes in parameters such as weight, fat mass, waist circumference, and exercise

performance compared with patients untreated with LT4, suggesting that LT4 also does not alter body

composition or muscle function in euthyroid individuals.

A recent meta-analysis has shown that LT4 is an ineffective treatment for obesity

Pollock MA, Sturrock A, Marshall K, Davidson KM, Kelly CJ, McMahon AD, McLaren EH 2001 Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the

reference range: randomised double blind placebo controlled crossover trial. BMJ 323:891–895.

Dubois S, Abraham P, Rohmer V, Rodien P, Audran M, Dumas JF, Ritz P 2008 Thyroxine therapy in euthyroid patients does not affect body composition or muscular function. Thyroid 18:13–19.

Jonklaas, Jacqueline, et al. “Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement.” Thyroid, vol. 24, no. 12,

2014, pp. 1670–1751., doi:10.1089/thy.2014.0028.

Kaptein EM, Beale E, Chan LS 2009 Thyroid hormone therapy for obesity and nonthyroidal illnesses: a systematic review. J Clin Endocrinol Metab 94:3663–3675

Kaptein EM, Beale E, Chan LS 2009 Thyroid hormone therapy for obesity and nonthyroidal illnesses: a systematic review. J Clin Endocrinol Metab 94:3663–3675.

EUTHYROID TREATMENT

ATA 10a. Is there a role for the use of levothyroxine to treat biochemically euthyroid patients with

symptoms that overlap with those of hypothyroidism?

We strongly recommend against the use of levothyroxine treatment in patients who have nonspecific symptoms

and normal biochemical indices of thyroid function because no role exists for use of levothyroxine in this

situation.

Strong recommendation. High-quality evidence.

10c. We recommend against the treatment of obesity with levothyroxine in euthyroid individuals due to a lack

of treatment efficacy for this condition



2014, pp. 1670–1751., doi:10.1089/thy.2014.0028.

ALTERNATIVES TO LEVOTHYROXINE

https://getrealthyroid.com/conversion-guide.html

Dessicated extract from

porcine thyroid gland

Each grain contains 38mcg

of T4 and 9mcg of T3

4:1 ratio

T4+T3 COMBINATION

In a double-blind, crossover trial by Hoang, TD et al.

Compared T4 and desiccated thyroid extract with doses adjusted to maintain a TSH level between 0.5 and

3.0 mU/L

No differences in symptoms and neurocognitive measurements between the two groups

49 percent of the patients preferred thyroid extract over T4

19 percent preferred T4 and 33 percent had no preference

Hoang TD, Olsen CH, Mai VQ, et al. Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study.

J Clin Endocrinol Metab 2013; 98:1982.

Hoang TD, Olsen CH, Mai VQ, et al. Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study.

J Clin Endocrinol Metab 2013; 98:1982.

CONCERNS REGARDING NATURAL DESSICATEDTHYROID

NDT has Has T4-to-T3 ratio of 4:1

Human thyroid ratios are T4-to-T3 of 13:1 to 16:1

Can lead to supraphysiologic levels of T3

Thyrotoxicosis risk - Peak levels of T3 right after dose which are hard to detect due to the shorter

half-life of T3

Ross, D. Treatment of primary hypothyroidism in adults. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019

Jackson IM, Cobb WE 1978 Why does anyone still use desiccated thyroid USP? Am J Med 64:284–288.

Lev-Ran A 1983 Part-of-the-day hypertriiodothyroninemia caused by desiccated thyroid. JAMA 250:2790–2791.

CONCERNS REGARDING NATURAL DESSICATEDTHYROID

Although Hoang et al. study showed patients tended to prefer NDT over T4

Followed 78 patients over only 16 weeks.

Powered for quality of life endpoints (which was negative), not safety endpoints

Ross, D. Treatment of primary hypothyroidism in adults. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019

Jackson IM, Cobb WE 1978 Why does anyone still use desiccated thyroid USP? Am J Med 64:284–288.

Lev-Ran A 1983 Part-of-the-day hypertriiodothyroninemia caused by desiccated thyroid. JAMA 250:2790–2791.

No published controlled long-term outcome trials of the use of desiccated thyroid extract.

Data does not suggest additional benefit from the addition of LT3 to LT4 replacement therapy.

Delivery of T4 is thought to be crucial for the developing fetal brain and replacement with NDT

includes T3 that does not get delivered to fetus

Thyroid extract should not be used during pregnancy.



2014, pp. 1670–1751., doi:10.1089/thy.2014.0028.


ATA Recommendation

Levothyroxine be considered as routine care for patients with primary hypothyroidism, in preference to use of thyroid extracts. Although there is preliminary evidence from a short-duration study that some patients may prefer treatment using thyroid extracts, high-quality controlled long-term outcome data are lacking to document superiority of this treatment compared to levothyroxine therapy. Furthermore, there are potential safety concerns related to the use of thyroid extracts, such as the presence of supraphysiologic serum triiodothyronine levels and a paucity of long-term safety outcome data.


Consistent with American Assoc of Clinical Endocrinologists statement


2014, pp. 1670–1751., doi:10.1089/thy.2014.0028.

CASE 3

55 yo lady new patient here to establish care. Was started on Armour thyroid after recent diagnosis

of hypothyroidism. She wants refill/continue Armour because she read that it is the more natural

option.

ABSORPTION ISSUES

Consider absorption issues in patients who require higher than expected doses

In a prospective, nonrandomized study treatment of H. pylori was associated with reduction of serum

TSH levels from 30.5 to 4.2 mIU/L in patients who were considered nonresponsive to high doses of

LT4

In another study, comparison of patients with gastritis, related either to H. pylori or atrophic gastritis,

with a reference group without gastric disorders showed that the daily LT4 requirement was up to

34% higher in those with gastritis (2.05 vs. 1.5 μg/kg/d)

ATA recommends Hpylori and celiac testing, treatment, and reeval of thyroid function

Bugdaci MS, Zuhur SS, Sokmen M, Toksoy B, Bayraktar B, Altuntas Y 2011 The role of Helicobacter pylori in patients with hypothyroidism in whom could not be achieved normal

thyrotropin levels despite treatment with high doses of thyroxine. Helicobacter 16:124–130.

Centanni M, Gargano L, Canettieri G, Viceconti N, Franchi A, Delle Fave G, Annibale B 2006 Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med 354:1787–

1795.

Jonklaas, Jacqueline, et al. “Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement.” Thyroid, vol.

24, no. 12, 2014, pp. 1670–1751., doi:10.1089/thy.2014.0028.

ABSORPTION ISSUES

Other factors for decreased absorption:

Advancing age

Obesity (body mass index [BMI]>40 kg/m2)

Ileum appears to be main site of LT4 absorption.

Although there are case reports of increased LT4 requirements after intestinal bypass surgery when studied

directly LT4 absorption appeared to be preserved after Roux-en-Y surgery

-Hays MT, Nielsen KR 1994 Human thyroxine absorption: age effects and methodological analyses. Thyroid4:55–64.

-Michalaki MA, Gkotsina MI, Mamali I, Markantes GK, Faltaka A, Kalfarentzos F, Vagenakis AG, Markou KB2011 Impaired pharmacokinetics of levothyroxine in severely obese volunteers. Thyroid 21:477–

481.

-Rubio IG, Galrao AL, Santo MA, Zanini AC, Medeiros-Neto G 2012 Levothyroxine absorption in morbidly obese patients before and after Roux-En-Y gastric bypass (RYGB) surgery. Obes Surg 22:253–258.

-Gkotsina M, Michalaki M, Mamali I, Markantes G, Sakellaropoulos GC, Kalfarentzos F, Vagenakis AG, Markou KB 2013 Improved levothyroxine pharmacokinetics after bariatric surgery. Thyroid23:414–419.

MYXEDEMA COMA

Severe hypothyroidism

Hallmarks of myxedema coma are decreased mental status and hypothermia, but hypotension,

bradycardia, hyponatremia, hypoglycemia, and hypoventilation are often present as well

It is a medical emergency with a high mortality rate.

Mortality rate is high, ranging from 30 to 50 percent

Hylander, Britta, and Urban Rosenqvist. “Treatment of Myxoedema Coma Factors Associated with Fatal Outcome.” Acta Endocrinologica, vol. 108, no. 1, 1985, pp. 65–71., doi:10.1530/acta.0.1080065.

MYXEDEMA COMA

Typically present with confusion with lethargy and obtundation.

Also can have prominent psychotic features, (myxedema madness)

Progresses to coma if further left untreated

Westphal, Sydney A. “Unusual Presentations of Hypothyroidism.” The American Journal of the Medical Sciences, vol. 314, no. 5, 1997, pp. 333–337., doi:10.1097/00000441-

199711000-00011.

MYXEDEMA COMA

Workup includes

TSH and free thyroxine (FT4)

Cortisol

Westphal, Sydney A. “Unusual Presentations of Hypothyroidism.” The American Journal of the Medical Sciences, vol. 314, no. 5, 1997, pp. 333–337., doi:10.1097/00000441-

199711000-00011.

MYXEDEMA COMA TREATMENT

Levothyroxine 200 to 400 mcg intravenously, followed by daily doses of 50 to 100 mcg

T3 5 to 20 mcg intravenously, followed by 2.5 to 10 mcg every eight hours.

Hydrocortisone 100 mg intravenously every eight hours until exclusion of possible adrenal

insufficiency.

Supportive measures

If myxedema coma is suspected, treatment should be instituted without waiting for laboratory

confirmation.

Ross, D. Myxedema Coma. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019.

THYROID OVERVIEW

Labs TSH, FT4, Total T3

Hyperthyroid

Severity

Long term vs Short term

TSI/TRAB Graves

Uptake Scan

History

Pain

Pregnancy

Treat or observe

Beta blockers, methimazole, +/- steroids

Hypothyroidism

Severity

Etiology (primary vs secondary)

Start replacement (levothyroxine first line)

Refer to endocrinology anytime

Thank you for your time and interest

thyroid health449 graves’ patients receiving mmi or ptu, 24% developed a cutaneous reaction 3.8%...

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