Hyperthyroidism

Radioactive iodine therapy (RAI) & hyperthyroidism

* Damages/destroys thyroid tissue * Effects evident after 2-3 months * Treated w/ antithyroid drugs & Inderal before & during 1st 3 months of Tx * High incidence of post-tx hypothyroidism * Need for lifelong thyroid HRT

Most obvious clinical manifestations of hyperthyroidism:

* Goiter, bruits * Exophthalmos: 20-40% with Graves

Other SxS of hyperthyroidism

* Heat intolerance * Increased sensitivity to stimulant drugs * Elevated basal temp

Nutrition needs with hyperthyroidism:

* High calorie diet: 4,000-5,000/day for hunger & prevention of tissue breakdown * Protein allowance: 1-2 g/kg ideal body weight * Avoid caffeine, highly seasoned foods, high-fiber foods * Refer to dietician

Symptoms of Thyrotoxic crisis:

* Increased HR & Temp * Restlessness * Agitation * Seizures * Abdominal pain * N/V/D * Coma

GI symptoms of hyperthyroidism:

* Increased appetite, thirst * Weight loss * Diarrhea * Splenomegaly * Hepatomegaly

Beta-adrenergic blockers & hyperthyroidism:

* Relieve symptoms of thyrotoxicosis resulting from B-adrenergic receptor stimulation * Propanolol (Inderal) is given w/ other antithyroid drugs * Tenormin preferred when client has heart disease &/or asthma

CV system symptoms of hyperthyroidism:

* Systolic HTN * Increased cardiac output * Arrhythmias * Cardiac hypertrophy * Atrial fibrillation

Causes of hyperthyroidism:

* Thyroiditis * Nodular goiter * Exogenous iodine excess * Pituitary tumors * Thyroid cancer

What are the signs and symptoms consistent with all causes of hyperthyroidism?

- Heat intolerance - weight loss - tremor - difficulty sleeping - anxiety - irritability - flushed skin - Tachycardia, A. Fib in elderly

TFTs for hyper

- LOW TSH levels (neg feedback) - HIGH free (unbound) T4 levels

3 Tx options for hyperthyroidism:

* Antithyroid meds * RAI therapy * Subtotal thyroidectomy

Both MMI and PTU must be stopped ____ days prior to a thyroid scan, Tx with 131-Iodine, and a radioactive Iodine uptake test.

5 days

Graves' disease

An autoimmune disease w/ no known cause: antibodies developed to work against TSH * Hyperthyroidism/thyroid storm occur together * Diffuse thyroid enlargement, excessive TH secretion * May destroy thyroid tissue --> hypothyroidism

Carbimazole

- first choice - start with 15-40mg daily (depending on symptom severity) - maintain until TFTs normal (4-8weeks) - maintenance for 12-18mos --> decrease by 25-30% monthly, until 5-15mg - longer term treatment may be required if relapse

Which antibodies are increased in Graves' disease?

- TRAb, an IgG (binds and stimulate TSH-R) - also TPO in 80% of patients

Hyperthyroidism (Grave's Disease)

- autoimmune - antibodies to TSH receptor stimulate gland - increased production of thyroid hormones - 2% women, 0.2% men

Drug-induced agranulocytosis

- both can cause bone marrow suppression - decreased WBC-> infection - 0.3-0.5%= abrupt onset & not dose related - CSM warning BNF

Drug therapy for hyper

- carbimazole (active metabolite, methimazole) & propylthiouracil - interferes with thyroid hormone synthesis - preferred for children, pregnancy, breast feeding, uncomplicated disease in young adults

Patient Counselling for hyper

- carbimazole as single daily dose - duration of treatment - tapering to maintenance dose - report signs of agranulocytosis: sore throat, mouth ulcers, bruising - report signs of hepatic dysfunction: pruritis, jaundice, dark urine - need for reg review, tests - management of relapse

ACUTE stage of hyperthyroidism

- do NOT do radioactive iodine, or surgery due to thyrotoxic crisis (thyroid storm) - high amounts of thyroxine in blood - therefore DON'T do this too early

Treatment & therapy for Thyrotoxicosis is aimed at what acheiving what ends:

* Decreased thyroid hormone levels & symptoms * Fever reduction * Adequate hydration (fluid replacement) * Managing stressors

Precipitating factors leading to Graves disease

* Depleted iodine supply * Infection * Stressful life events + genetic predisposition

Musculoskeletal symptoms of hyperthyroidism:

* Fatigue * Muscle weakness * Proximal muscle wasting * Dependent edema * Osteoporosis

Neuro symptoms of hyperthyroidism:

* Fine tremors * Insomnia * Labile mood, delirium * Hyperreflexia of tendons * Inability to concentrate

Iodine & hyperthyroidism:

* Given concurrently w/ other antithyroid drugs to prepare for thyroidectomy or crisis Tx * Large doses rapidly inhibit T3, T4 synthesis & block their circulation * Decreases vascularity of thyroid gland * Maximal effect seen w/i 1-2 weeks * Long-term use is not effective

What are basic physiological effects of hyperthyroidism?

* Increased metabolism * Elevated hormones increase tissue sensitivity to stimulation by SNS by increasing the # of Beta-adrenergic receptors

Diagnosing hyperthyroidism:

* Measure lab values: TSH & free thyroxine (T4) * RAI uptake indicated to differentiate Graves disease from other forms of thyroiditis

Reproductive symptoms of hyperthyroidism:

* Menstrual irregularities * Amenorrhea * Decreased libido * Impotence * Gynecomastia * Decreased fertility

Integumentary symptoms of hyperthyroidism:

* Warm, smooth, moist skin * Thin, brittle nails * Hair loss * Clubbing of fingers * Diaphoresis * Vitiligo

Which of MMI or PTU is the preferred agent in children and during pregnancy?

*PPP*: PTU is the Preferred agent in Pregnancy. Less chance of hepatotoxicty.

What is the usual course of PPT?

- 1st - 6th month = hyperthyroid (T4/T3 suppress TSH) - 2nd - 8th month = hypothyroid (T4/T3 fall) - Recovery

Propylthiouracil

- 200-400mg daily initially, in divided doses - 50mg tid maintenance - pregnancy & breast feeding (? slightly safer) - intolerant of carbimazole (rash, agranulocytosis)

SE of both MMI and PTU include:

- Agranulocytosis / Neutropenia - Allergy - Rash - Rarely hepatotoxicity - Rarely nephrotoxicity

Features of Hyperthyroidism

- Anxious - Palpitations - Tremor - Weight loss - Tachy - Goitre--> specific: not universal - Prefers cold weather - Warm, moist skin **many nonspecific symptoms (thus differential= cancer)

MMI and PTU both decrease production of thyroid hormone. PTU can also _____________.

- Block the conversion of T4 to T3.

Block and Replace Therapy

- Carbimazole 40-60mg & 50-100mcg thyroxine - Carbimazole for approx. 4-8 weeks before start thyroxine - makes pt TEMPORARILY hypo - 6-12mos usually; up to 18mos - thyroid gland returns to normal function when stop treatment - relapse may occure - not in pregnancy (carbimazole crosses placenta--> baby can be impaired)

What signs and symptoms are specific to Graves' disease

- Exopthalmos (proptosis) - Graves dermopathy ("orange peel skin")

Iodine for drug-induced thyroid disease

- OD (ex radiographic contrast media) --> acute (inhibits release of T3/T4 from thyroid) --> prolonged (high doses) suppress T3/T4 production - rarely causes thyrotoxicosis if underlying defect in autoregulation - iodine deficiency (very rare) can cause hypo due to inability to produce T3/T4

Lithium

- for drug-induced hypothyroidism HYPO: - inhibits iodine uptake and prevents T3 & T4 release - can be transient and subclinical - monitor TSH - start replacement T4 therapy if clinical HYPER: - rare, paradoxical effect

Amiodarone

- for drug-induced thyroid disease HYPO: can occur anytime in trtmt --> inhibits synthesis and release of T3/T4 --> usually continue amiodarone and start replacement T4 therapy if necessary MILD HYPER: --> blocks conversion T4->T3; thus increases TSH and T4 --> transient when start trtmt; normalises in 3-4mos SEVERE HYPER: --> increased production of T4 b/c of iodine content --> direct thyroiditis: excessive treatment of iodine content --> withdraw therapy, if possible or may use carbimazole

Surgery

- for hyper - young age - intolerance to drug treatment - oesophageal obstruction

Radioactive Iodine (I-131)

- if fails to respond to drug treatment (or reduce goitre without surg) - relapse after surg - toxic nodular goitre - for hyper

CSM warning from BNF for carbimazole

- must recog bone marrow suppression induced by carbimazole, need to stop treatment promptly - patient should be asked to report symptoms and signs suggestive of infection (esp sore throat) - WCC performed if any clinical evidence of infection - carbimazole should be stopped if any clinical/lab evidence of neutropenia

What risks are increased after PPT?

- recurrent PPT in subsequent pregnancies - development of primary hypothyroid within 5-10 years

What are the 4 possible causes of hyperthyroidism? Which one is most common?

1) Graves Disease (most common) 2) Toxic multinodular goiter (autonomous thyroid nodules) 3) Toxic adenoma (solitary, benign thyroid tumor) 4) TSH-secreting pituitary adenoma

Treatment options for hyper (3)

1. Drug therapy- therapy&adjuvant treatment 2. Radioactive iodine 3. Surgery **none are ideal (involve patient in choice if possible)

Treatment options for drug-induced thyroid disease (3)

1. Iodine 2. Amiodarone 3. Lithium

The risks of untreated hyperthyroidism include(4):

1. Myopathy 2. Cardiac arrhythmias 3. Cardiomyopathy 4. Osteoporosis

Thyroid storm has many causes including (5):

1. Radioactive iodine 2. Infection 3. Trauma 4. Surgery 5. Withdrawal from antithyroid drugs.

Hyperthyroidism occurs with highest frequency in what age group?

30-50

Exophthalmos

An impaired drainage from the orbit with increased fat & edema in the retro-orbital tissues * Causes eyeballs to protrude * Corneal surfaces become dry & irritated

Adjuvant therapy for hyperthyroidism

BETA-BLOCKER - rapid relief of symptoms w/in 4 days: palpitations, anxiety, tremor - C/I asthma - propranolol, nadolol - may need 3-4/day as metabolism increased in hyper - usually needed for initial stages of treatment (first 8 wks) when pt still symptomatic; usually stopped

What is thyrotoxic crisis (thyroid storm) characterized by?

Fever Tachycardia Confusion N&V

What are toxic nodular goiters?

Nodules of the thyroid that secrete TH, independent of TSH Begin as follicular adenomas * Small autonomous nodules do not secrete enough to cause thyrotoxicosis, but large nodules may: > 3 cm

Thyrotoxicosis

Occurs as a result of hypermetabolism of excess T3 & T4 "Thyroid storm"

List 2 antithyroid drugs & their effects/usages

Propylthiouracil (PTU) & methimazole (Tapazole) * Inhibit synthesis of TH * Spontaneous remission occurs * Improvement begins in 1-2 weeks * Taken from 6 months to 2 years * Not curative * Shrinks thyroid before surgery to make surgery safer

In subclinical hyperthyroidism, TSH is suppressed while thyroid hormone levels are normal. Subclinical hyperthyroidism is common and can be a risk factor for ___________.

Risk factor for atrial fibrillation

What lab findings are consistant with clinical hyperthyroidism?

TSH low fT4 usually elevated fT3 elevated

Graves' disease is the ________ form of hyperthyroidism, accounting for ______ of cases.

The most common. 75% of cases

Hyperthyroidism: what is it?

This disorder involves a sustained increase in the production/release of thyroid hormones by the thyroid gland

Thyroid storm

Thyrotoxicosis * Acute rare condition: heightened symptoms of hyperthyroidism * Death rare w/ Tx, but can be deadly w/o * Caused by stressors

Overall, which gender experiences thyroid disorder more?

Women

What might be the mechanistic cause of proptosis?

cytokine production by infiltrating T cells

What is the cause of post-partum thyroiditis (PPT)?

autoimmune disorder