THYROID - cdn.ymaws.com

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The Endocrine System

Thyroid

THYROID Diagnosis and Treatment

Robert Ferraro, MD Medical Director Southwest Endocrinology Assoc. Albuquerque, NM

Overview •  Physiology •  Diagnostic Testing •  Pathology

– Hypothyroidism – Hyperthyroidism – Thyroid nodules – Thyroid cancer

•  Medical therapy

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Thyroid - Anatomy

Thyroid - Physiology


1 - thyroid follicle 2 - cavity of the thyroid follicle, filled with colloid 3 - blood vessel 4 - parafollicular cells forming interfollicular clumps

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•  Functions of thyroid homone: –  important in regulating body energy, –  the body's use of other hormones and vitamins, and –  the growth and maturation of body tissues.

Thyroid – Symptoms

Symptoms of Hypothyroidism fatigue, exhaustion feeling run down and sluggish depression difficulty concentrating, brain fog unexplained or excessive weight gain dry, coarse and/or itchy skin dry, coarse and/or thinning hair feeling cold, especially in the extremities constipation muscle cramps increased menstrual flow more frequent periods infertility/miscarriage

Thyroid - Symptoms

Symptoms of Hyperthryoidisim nervousness irritability increased perspiration thinning of your skin fine brittle hair muscular weakness especially involving the upper arms and thighs shaky hands panic disorder insomnia racing heart more frequent bowel movements weight loss despite a good appetite lighter flow, less frequent menstrual periods

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Thyroid – Diagnostic studies

•  Physical exam •  Thyroid function tests •  Imaging studies

–  Ultrasound –  Nuclear Medicine

•  Radio-iodine uptake •  Thyroid scan

Thyroid – thyroid function tests

Thyroid – Diagnostic imaging

Thyroid Ultrasound

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Thyroid - Ultrasound

Thyroid – Nuclear medicine

Thyroid scan

Thyroid – Physical exam

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Thyroid - Cases

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Thyroid - Pathophysiology

Hypothyroidism Primary – Autoimmune thyroid disease

(Hashimoto’s thyroiditis) – Post-surgical – Post-radioiodine treatment

Secondary

– Pituitary tumor – Pituitary surgery/radiation

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Thyroid - Hypothyroidism

Diagnosis

Clinical symptoms: Physical findings: Laboratory findings:

Thyroid – Hyperthyroidism

Causes –  Autoimmune

(Grave’s disease) –  Toxic thyroid nodule/toxic mutinodular

thyroid – Iatrogenic – Factitious – Iodine induced – Medication side effects

Thyroid - Hyperthyroidism

Diagnosis Clinical symptoms: Physical findings: Laboratory findings:

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Thyroid – Case stories - #1

24 y/o female referred for evaluation of abnormal thyroid functions and possible hyperthyroidism. –  Asymptomatic - Med Hx - neg –  PE – normal - Meds: Vitamins, OCP’s –  Thyroid functions:

•  Total T4 elevated

–  What next steps for diagnosis? •  Labs •  Imaging

–  Diagnostic differential –  Treatment


52 y/o female referred for management of thyroid hormone replacement therapy. Her dosage has fluctuated between 0.075 mg and 0.125 mg daily over the past 3 years. Her TSH has fluctuated between 0.04 uIU/ml and 8 uIU/ml. In past 6 months, her dosage has remained constant, 0.100 mg daily, but her TSH has varied, with each measurement, every 2 months: 8/2010 - 1.0 uIU/ml 10/2010 - 0.05 uIU/ml 12/2010 – 8.0 uIU/ml

What additional history do you need?


•  Factors which can affect thyroid hormone absorbtion –  Food –  Drugs

•  Calcium, vitamins •  Cholestyramine •  Ferrous sulfate •  Sulcrafate •  Antacids with aluminum hydroxide

•  Factors which accelerate levothyroine metabolism –  Drugs

•  Anticonvulsants •  Rifampine •  Sertraline (Zoloft)

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•  76 y/o male with Type II diabetes, insulin requiring, whose TSH has been consistently below normal, although the free T4 and free T3 are normal, for the past 4 months: 12/2010 - 0.02 uIU/ml 3/2011 - 0.05 uIU/ml He is asymptomatic and his physical exam is normal. What additional clinical or physical data do you need? What is the operative diagnosis? What is the next diagnostic study?

Thyroid – Nuclear medicine

Thyroid scan


32 y/o female referred for evaluation and management of nodular thyroid disease and hyperthyroidism. She has the following symptoms: -15 lb unintentional weight loss over the past 3 yrs. - anxiety - insomnia - diffuse muscle pain - intermittent palpitations

Previous nuclear medicine studies (1 year earlier) reveal normal uptake at 24 hours, but the scan revealed various hot nodules and several large “cold” defects.

PE: normal pulse, neg goiter, mildly hyperreflexic

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What are your impressions? What is the next diagnostic study? What are the treatment options?


34 y/o female self-referred because she is convinced she has a metabolic disorder. Her complaints: - hair falling out “by the handful”. - 15 lb unintentional weight gain over past year, with no significant change in lifestyle. - can’t focus or concentrate, this is affecting performance at work. - mild dysthymia - hands and feet are always cold.

She has no labs to review. PE: normal

What is the next diagnostic study?


Labs: CBC, CMP were normal. TSH = 4.9 uIU/ml (nl range: 0.4 – 4.2 uIU/ml) Free T4 = 0.8 ng/dl (nl range: 0.8 – 3.2 ng/dl)

Impressions?

Additional diagnostic studies? Treatment options?

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Thyroid – Subclinical Thyroid Disease

Consensus Development Conference* (AACE, ATA and Endocrine Society) “Proper diagnosis and treatment of

subclinical throid disease”

Subclinical Hypothyroisim –  Paucity of evidence-based data –  TSH limit should remain 4.5 uIU/ml rather then 3.0-3.5 as

some other organizations have suggested –  Since the available data do not show clear-cut benefit

from early thyroxine therapy, routine treatment for patients with TSH between 4.5 and 10 uIU/ml is not warranted.

* JAMA 2004; 291:228-238

Thyroid – Subclinical Thyroid Disease

Subclinical Hyperthyroidism –  The report concluded that it is reasonable to treat

patients with TSH <0.1. –  Those with TSH between 0.1 and 0.45 uIU/ml should be

monitored but not treated.


Labs: CBC, CMP were normal. TSH = 4.9 uIU/ml (nl range: 0.4 – 4.2 uIU/ml) Free T4 = 0.8 ng/dl (nl range: 0.8 – 3.2 ng/dl)

Impressions?

Additional diagnostic studies? Treatment options?

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Thyroid – AACE* guidelines

AACE guidelines differs in several areas with the Consensus statement: –  The upper limit of normal for TSH should be 3.0 uIU/ml –  Anti-thyroid antibodies should be measured in patients with

subclinical hypothroidism –  AACE recommends treatment of patients with TSH >5.0 uIU/

ml if: •  Goiter present •  Anti-thyroid antibodies present •  Patient is symptomatic •  Pregnancy or imminent pregnance

The provider who has performed an exam and history should

decide on the treatment of each individual patient

* American Association of Clinical Endocrinolology


45 y/o male with 3 month history of palpitations, 20 lb unintentional weight loss, heat intolerance and insomnia. PCP referred after getting thyroid functions. The TSH was suppressed, the free T4 was elevated and the free T3 was markedly elevated.

PE: pulse was 110 at rest, he had a prominent diffuse goiter, there was a bruit over the thyroid, he was tremulous and hyperreflexic. He had a wide eyed stare with upper lid restraction but no proposis.

Impression? What additional diagnostic studies would be helpful to

confirm your diagnostic impression?


What treatment options do you have?

Should you wait for any confirmatory studies or can you treat now? What medications would you prescribe?

What is the risk of sending this patient to nuclear medicine for definitive therapy now?

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42 y/o female with longstanding history of hypothyroidism, currently treated with Synthroid 0.088 mg daily. She takes her medication “religiously” on an empty stomach, 1 hour before any food or vitamins/minerals. Her TSH is consistenly normal, 1.8-2.2 uIU/ml.

In the past 6 months she has been feeling more fatigued, particularly in the afternoons, is having more trouble concentrating and often feels that she has “foggy brain”. Her weight is up 5 pounds and she can’t seem to exercise like she used to.

Her metabolic workup is completely normal. Impressions?


Patient was referred to endocrinology for further evaluation and management.

Plan: trial with combination T3/T4 therapy.

–  Start liothyronine 5 ug tabs, 1 tab daily for 1 week and if tolerated, increase to 2 tabs (10 ug) daily, in the AM.

–  Decrease Synthroid to 0.075 ug daily. –  Repeat TSH in 4 weeks with follow-up.

Response: –  Patient feels 100% better; –  TSH was 1.5 uIU/ml. –  Plan: continue combination therapy and recheck TSH in

2 months then annually

Thyroid – Controversies

•  Treatment with combination T3 plus T4 –  AACE and ATA guidelines both state that there is a

paucity of large scale, randomized prospective studies of combination therapy.

–  Therefore, there is insufficient evidence to know which patient with hypothyroidism would be better treated with a combination of T4 plus T3 rather than with T4 alone.

•  Generic vs Branded levothyroxine –  AACE recommends the use of high-quality brand

preparations of levothyroxine

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Brand vs generic cont’d

AACE, ATA and TES issued a joint statement regarding the use and interchangeability of

Thyroxine products in 2004.*

–  The FDA acknowledged concerns about its method for determining bioequivalence

–  The FDA has not changed its methodology and has proceeded to grant generic status to a a variety of levothyroxine preparations.

–  Patients and many physicians are unaware of these concerns

* AACE website home page – Quick Links – AACE Position statements #6


BEST MEDICAL PRACTICE •  Patient should be maintained on the same

brand name levothyroxine product.

•  If the brand is changed, from a brand to another brand or to a generic or from a generic to another generic, then TSH needs to be remeasurred 6 weeks later and the drug should be retitrated as needed.


•  Levothyroxine vs Armour thyroid –  Biological (Armour thyroid) and synthetic thyroid

hormone preparations containing both T4 and T3 (Thyrolar) are also not currently recommended for therapy since they produce fluctuating and often elevated T3 concentrations, although their use is not necessarily contraindicated

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Thyroid – in Pregnancy

•  Hypothyroidism –  Thyroid hormone requirements are higher in

pregnancy and dosages need to be titrated to maintain a normal level

•  Hyperthyroidism –  Treatment with anti-thyroid medications –  PTU most commonly used, although

methimzole can be used and is more convenient

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