Hyperthyroidism

Case 12 Garrett P. Paltao

Problem List
1) 2) 3) 4) 5) Graves disease Thyroid storm Opthalmopathy Pretibial myxedema Pernicious anemia

 is characterized by a breakdown in self-tolerance to thyroid auto-antigens, most importantly the TSH receptor. The result is the production of multiple autoantibodies like Thyroid-stimulating immunoglobulin It is characterized by a triad of clinical findings: 1) Hyperthyroidism due to diffuse, hyperfunctional enlargement of the thyroid 2) Infiltrative ophthalmopathy with resultant exophthalmos 3) Localized, infiltrative dermopathy, sometimes called pretibial myxedema, which is present in a minority of patients

Graves Diseases

Thyroid Storm
- is rare and presents as a life-threatening exacerbation of hyperthyroidism, accompanied by fever, delirium, seizures, coma, vomiting, diarrhea, and jaundice. - The mortality rate due to cardiac failure, arrhythmia, or hyperthermia is as high as 30%, even with treatment. - Thyrotoxic crisis is usually precipitated by acute illness (e.g., stroke, infection, trauma, diabetic ketoacidosis), surgery (especially on the thyroid), or radioiodine treatment of a patient with partially treated or untreated hyperthyroidism.

Graves Diseases and Thyroid Storm

Basis: A. Chief complaint 1) Generalized weakness 2) Shakes- tremors 3) Feeling of Burning up Heat Intolerance 4) Palpitation 5) Intermittent Chest Pain 6) Shortness of breath 7) Swelling in feet

B. HPI 1) Anxious ,forgetful, confused 2) Frequent diarrhea 3) No period in 4 months Oligoamenorhea 4) Loss of 7 kg over the past few months 5) Ravenous appetite 6)Eyes is protruding- Opthalmopathy 7) Px takes PTU only once or twice a day because she forgets to take it and thinks it causes diarrhea and itchy rash all over

C. Past medical history Previously diagnosed with Graves disease (2 yrs ago) Complicated by opthamopathy , pretibial myxedema and pernicious anemia There is a history of Thyroid storm secondary to non adherence to therapy D. Family and Social History Grandmother with Graves disease and opthalmopathy Drinks beer intermittently when anxious; live with BF

E. Medication History 1) PTU- 200 mg PO q6h (taken sporadically) 2) Vitamin B12 3) Pseudonephrine 4) Diphenhydramine 5) Ethinyl estradiol and norethrindone
F. Allergies Cephalexin- rash

G. Physical Examination GEN: Tremulous, anxious and restless female in apparent respiratory distress, intermittently stuporous V.S. BP- 180/ 100, HR- 130, RR- 28 T- 40 C Wt-52 kg Ht-170 cm HEENT: Thin, fine hair with patches of baldness; R>L; (+) lid lag; (+) stare; (+)chemotasis and conjunctivitis; (+) painful tongue; diffusely enlarged goiter 5 times normal size; (+) bruit in right thyroid lobe; (+) JVD COR: Rapid irregular rhythm; (+) S3 and (+)S4; displaced PMI CHEST Bilateral rales and crackles

ABD: Soft (-) masses, (+) abdominal tenderness; hepatomegaly; hyperdynamic bowel sounds GU: WNL RECT: Guiac negative EXT: 2 + pitting edema bilaterally; (+) pretibial myxedema; hot flushed skin with fine maculopapular rash; (+) palmar erythema and onycholysis NEURO: Rapid DTRs with mild clonus; decreased pinprick and vibratory sensation in lower legs; weakness of large muscle groups; (+) coarse tremors

H. Pertinent Laboratory Tests Na- 130 (135- 145) K- 3.2 (3.6- 5.2) Cl- 90 (100- 108) Crea- 133 (M: 0.8- 1.3; F:0.6- 1.1) Hct- 0.23 (M: 42- 52; F: 36-42) Hb- 80 (M:120-140; F: 140- 170) Leu- 14.3 x 109 (5- 10) T Bili- 60 (1.7- 17.1) Glu- 6.7 (4.2- 6.1) PT- 15 (8.3-10.8)

TT4- 257 nmol/L (70-151) TT3-12.7 nmol/L (1.2- 2.1) FT4i- 121 mmol/L (1.34.2) TSH- <0.05 mU/L (0.34- 4.25) ATgA- positive Vit B12- 59 pmol/L (206-735)

CXR: Cardiomegaly; Pulmonary Edema ECG: HR 130-150 atrial fibrillation, (+) LVH

Treatment Objectives
1) Identification and treatment of the precipitating cause and other co-morbid conditions that contribute to the current problem of the patient 2) Provide drugs that can reduce thyroid hormone synthesis 3) Intensive monitoring and supportive care 4) To impose strict compliance of the medication by the patient.

EMERGENCY TREATMENT

Large doses of propylthiouracil. the drug's inhibitory action on T4 T3 conversion makes it the antithyroid drug of choice

Stable iodide is given to block thyroid hormone synthesis via the WolffChaikoff effect

Propranolol should also be given to reduce tachycardia and other adrenergic manifestations

Additional therapeutic measures include glucocorticoids

Non- Pharmacologic
1) Give antibiotics if infection is present 2) Cooling (Cooling blankets, Cold sponge bath) 3) Oxygen therapy 4) intravenous fluids and electrolytes for proper hydration and to correct electrolyte imbalances.

Pharmacologic
Medication Summary 1)Drugs that ameliorate hyperadrenergic effects of thyroid hormone on peripheral tissues 2)Drugs that decreases further synthesis of thyroid hormone 3)Drugs that decreases hormonal release from the thyroid 4)Drugs that prevent further TH secretion and peripheral conversion of T4 to T3

Drugs that decreases further synthesis of thyroid hormone

Propylthiouracil Methimazole

Efficacy
Safety Suitability Cost

+++
+++ +++ +++

++
++ ++ ++

Propylthiouracil
DOC that inhibits synthesis of TH by preventing organification and trapping of iodide to iodine and by inhibiting coupling of iodotyrosines; also inhibits peripheral conversion of T4 to T3, an important component of management.

Pharmacology Absorption: 75% Half-Life: 1-2 hr, incr in ESRD Vd: 0.4 L/kg Protein Bound: 75-80% Peak Plasma Time: 1-1.5 hr Peak Plasma Concentration: (200-400 mg single dose): 6-9 mcg/mL Metabolism: liver, to glucuronide conjugates, inorganic sulfates, sulfur metabolites Total Body Clearance: 7 L/hr Excretion: urine (35%)

Hyperthyroidism 300-450 mg/day PO divided q8hr initially (may require up to 600-1200 mg/day) Maintenance: 100-150 mg/day divided q8hr Thyrotoxic Crisis Initial 200 mg PO q4-6hr initially on Day 1, then reduce gradually Maintenance dose 100-150 mg/day divided BID/TID

 Adverse Effects 1-10% Polyarthritis <1% Agranulocytosis Dermatologic reactions Hepatitis

Drugs that ameliorate hyperadrenergic effects of thyroid hormone on peripheral tissues

Propanolol Esmolol ++ +++ ++

Efficacy Safety Suitability

+++ ++ +++

Cost

Propranolol
DOC most widely used in this group; It is a nonselective betaadrenergic antagonist. Decreases heart rate, myocardial contractility, BP, and myocardial oxygen demand. Often the only adjunctive drug needed to control thyroid storm symptoms.

Pharmacokinetics Excretion: Feces (55-60%); urine (40%) Duration: 6-12 hr for immediate release; 24-27 hr extended release Peak Plasma Time: 1-4 hr (immediate release), 6-14 hr (extended release) Bioavailability: 30-70% Protein Bound: 68% (newborns); 90% (Adults) Vd: 4 L/kg in adults Metabolism: Hepatic P450 enzyme CYP2D6 and CYP1A2 Metabolites: 4-hydroxypropranolol (active)

 Supraventricular Arrhythmia 10-30 mg PO q6-8hr IV: 1-3 mg/dose IV at 1 mg/min initially; repeat q25min to total of 5 mg Once response or maximum dose achieved do not give additional dose for at least 4 hr

Adverse Effects Aggravated CHF Bradyarrhythmia Hypotension Contraindications Asthma/COPD Sinus bradycardia, 2/3 heart block Cardiogenic shock

Drugs that decreases hormonal release from the thyroid

Potassium iodide, saturated solution (Pima, SSKI, Thyro-Block) This agent is used to inhibit TH release from the thyroid gland. One mL of SSKI contains 1 g of potassium iodide or 750 mg of iodide (ie, approximately 50 mg iodide/drop and 15 drops per mL). Because of the viscosity, SSKI comes as 15 drops per mL rather than the usual 20 drops per mL.

Mechanism of Action Hyperthyroidism: Suppresses thyroid hormone synthesis (via the Wolff-Chaikoff effect) Thyroid protective: Systemically circulating potassium iodide is readily taken up by thyroid gland by sodium/iodide transporter in basal membrane; concentration gradient of thyroid gland to plasma is 20-50:1 Expectorant: Iodine helps to increase respiratory secretions and decrease viscosity

Pharmacology Distribution: Significant extracellular distribution, with most accumulation in thyroid gland Onset: Therapeutic effects observed within 24 hr Maximum Effect: After 10-15 days of therapy Duration of Effect: Therapeutic effect may persist up to 6 weeks after chronic administration Metabolism: unknown Excretion: renal

Dosages Thyrotoxic Crisis 250-500 mg (5-10 gtt of 1 g/mL) PO q4hr Preoperative Thyroidectomy 50-250 mg (1-5 gtt of 1 g/mL) PO TID for 10-14 days
Adverse Effects (Frequency Not Defined) Arrhythmia Skin rash Gastrointestinal irritation or bleeding

Drugs that prevent further TH secretion and

peripheral conversion of T4 to T3
Corticosteroids These agents block conversion of T4 to T3. The use of corticosteroids has been associated with improved survival. Stress doses are required to replace accelerated production and degradation of cortisol induced by TH. If corticosteroids are not administered, acute glucocorticoid deficiency hypothetically could occur because demand may outpace production.

Hydrocortisone

Dexamethasone +++ ++ ++ +++

Radioactive Iodine +++ + + +

Efficacy Safety Suitability Cost

+++ +++ +++ +

Hydrocortisone (Solu-Cortef) Hydrocortisone provides mineralocorticoid activity and glucocorticoid effects and may help ameliorate decreased adrenal reserve. It reduces the conversion of T4 to T3. Mechanism of Action Controls or prevents inflammation by controling the rate of protein synthesis, suppressing migration of PMNs & fibroblasts, & reversing capillary permeability

Pharmacology Half-Life: Plasma: 1-2 hr, biological: 8-12 hr Duration: short-acting Bioavailability: PO: 96% Protein Bound: 90% Vd: 34 L Metabolism: in tissues & liver to inactive glucuronide & sulfate metabolites Metabolites: glucuronide & sulfate metabolites (inactive) Excretion: mainly in urine, minimally in bile

Adrenal Insufficiency (Acute) IM/IV: 100 mg IV bolus, THEN 300 mg/day divided q8hr OR cont. infusion x 48 hours When stable change to oral: 50 mg PO q8hr x 6 doses, THEN taper to 30-50 mg/day divided doses PO Contraindications Untreated serious infections Hypersensitivity

Dr. Garrett P. Paltao MD,FPSGS, FPCS Cardio-Thoracic Surgeon St. Luke's Hospital, Quezon City Tel. 643-89-09 Name of patient: C,D Age: 30 Address: Pasig City Sex: F Rx: Date: 7/19/12 Prophylthiouracil, (Rhea PTU) 200 mg/ tab # 28 tablets Take1tablet every 6 hours orally for 1 week Propanolol (Inderal) 20mg/tab #28 tablets Take1tablet every 6 hours orally for 1 week

Note: For follow up after 1 week (7/26/12)

Garrett P. Paltao M.D. Lic. NO. 0054424 PTR NO. 0506055 S2 Lic. NO. 05143