Management of Hyperthyroidism Dr Mojgan Sanjari Associate Professor of endocrinology and metabolism Kerman university of medical sciences 2017/20/04

Outlines: Case presentation Possible differential diagnosis Treatment options Based on : 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis And www.thelancet.com Vol 388 August 27, 2016

Hypothetical patient Patient is a 28 year old nurse referred to you by gynecologist due to abnormal TSH. She complains palpitation , fatigue and mild weight loss since 2 weeks ago . She had cesarean section 10 weeks ago and common cold 2 weeks ago. She is not on medication .Positive history of hashimoto thyroiditis in her sister. Physical exam has no significant finding except tachycardia and thyroid enlargement, most prominent in left lobe.

Causes of thyrotoxicosis Thyrotoxicosis associated with a normal or elevated RAIuptake over the neck Graves Disease Toxic Adenoma or TMNG Trophoblastic disease TSH-producing pituitary adenomas Resistance to thyroid hormone (T3 receptor beta mutation,THRB)

Thyrotoxicosis associated with a near-absent RAI uptake over the neck Painless (silent) thyroiditis Amiodarone-induced thyroiditis Subacute (granulomatous, de Quervain’s) thyroiditis Palpation thyroiditis Iatrogenic thyrotoxicosis Factitious ingestion of thyroid hormone Struma ovarii Acute thyroiditis Extensive metastases from follicular thyroid cancer

Hypothetical patient Patient is a 28 year old nurse referred to you by gynecologist due to abnormal TSH. She complains palpitation , fatigue and mild weight loss since 2 weeks ago . She had cesarean section 10 weeks ago and common cold 2 weeks ago. She is not on medication .Positive history of hashimoto thyroiditis in her sister. Physical exam has no significant finding except tachycardia and thyroid enlargement, most prominent in left lobe.

Determination of etiology(R1) Depending on available expertise and resources, Measurement of TRAb, Determination of the radioactive iodine uptake (RAIU) Measurement of thyroidal blood flow on ultrasonography. A 123I or 99mTc pertechnetate scan should be obtained when the clinical presentation suggests a TA or TMNG. Strong recommendation, moderate-quality evidence.

Symptomatic management(R2) Beta-adrenergic blockade: Symptomatic thyrotoxicosis, Elderly patients Resting heart rates in excess of 90 beats per minute Coexistent cardiovascular disease. Strong recommendation, moderate-quality evidence

Beta-Adrenergic Receptor Blockade in the Treatment of Thyrotoxicosis

How should overt hyperthyroidism due to GD be managed?(R3) Patients with overt Graves’ hyperthyroidism should be treated with any of the following modalities: RAI therapy, ATDs, or Thyroidectomy Strong recommendation, moderate-quality evidence

Anti Thyroid drug: Patients with high likelihood of remission (patients, especially women, with mild disease, small goiters, and negative or low-titer TRAb); Pregnancy; The elderly or others with comorbidities increasing surgical risk or with limited life expectancy; individuals in Nursing homes or other care facilities Patients with previously operated or irradiated necks; Patients with lack of access to a high-volume thyroid surgeon; Patients with moderate to severe active GO; and Patients who need more rapid biochemical disease control

Side-effects Minor side-effects of ATDs occur in about 5% of patients. These side-effects include pruritus, arthralgia, and gastrointestinal distress. In patients with minor skin reactions, an antihistamine can be added or one ATD can be substituted for the other

Major side-effects of ATDs: Agranulocytosis, in which the absolute granulocyte count is less than 500 cells/mm3, is the most frequent major side-effect. Patients usually present with fever or sore throat, or both, and sometimes chills, diarrhea, and myalgia. The annual incidence of agranulocytosis has been estimated to be 0・1–0・3%and generally occurs within 90 days after initiation of therapy.

Agranuolocytosis: When patients receiving ATDs present with these symptoms, a white blood cell count with differential should be obtained and the ATD should be immediately discontinued if the granulocyte count is less than 1000 cells/mm3. Treatment of agranulocytosis and its associated infections might be also necessary, such as administration of broad-spectrum antibiotics and granulocyte colony-stimulating factor , which has been shown to reduce the recovery time.

Hepatotoxicity occurs in 0・1–0・2% of patients. It usually develops within 3 months of therapy incidence peaks in the first 30 days of treatment. The ATA/AACE guidelines recommend: Obtaining a serum liver profile at baseline , but recommend against periodic monitoring unless the patient complains of symptoms of hepatic dysfunction, such as pruritic rash, jaundice, light-coloured stool, or dark urine.

Patients at higher risk of recurrence are: Those with severe hyperthyroidism, Large goitre, High T3:T4 ratios, Persistently suppressed TSH, and high baseline concentrations of TRAb.

RAI therapy: Women planning a pregnancy in the future(>6months) Comorbidities increasing surgical risk, Previously operated or externally irradiated necks, lack of access to a high-volume thyroid surgeon, contraindications to ATD use or failure to achieve euthyroidism during treatment with ATDs. Periodic thyrotoxic hypokalemic paralysis, Right heart failure Pulmonaryhypertension, or Congestive heart failure

Surgery: Women planning a pregnancy in <6 months Symptomatic compression or large goiters (‡80 g); relatively low uptake of RAI; when thyroid malignancy is documented or suspected (e.g., suspicious or indeterminate cytology); Large thyroid nodules especially if greater than 4 cm or if nonfunctioning, or hypofunctioning coexisting hyperparathyroidism and patients with moderate to severe active GO.

If surgery is chosen as treatment (R24):for GD, patients should be Rendered euthyroid prior to the procedure with ATD pretreatment, with or without b-adrenergic blockade. A KI containing preparation should be given in the immediate preoperative period. Strong recommendation, low-quality evidence

Following thyroidectomy for GD: L-thyroxine should be started at a daily dose appropriate for the patient’s weight(0.8 µg/kg or 1.6 µg/kg), with elderly patients needing somewhat less, Serum TSH measured 6–8 weeks postoperatively. Strong recommendation, low-quality evidence

Take home message: In patients with symptoms of hyperthyroidism consider all causes of thyrotoxicosis . If any doubt check TRAB, RAIU, Thyroid ultrasonography or scan Long term ATD , Surgery or Radioablation can be used for treatment of hyperthyroidism.

Thanks for your attention Question or comments Thanks for your attention