What is Thyrotoxicosis? Case of child who ingest large dose of levothyroxin which lead to toxicity.

1. THYROID
SUPPLEMENT
INGESTION

2. THYROTOXICOSIS
• THYROTOXICOSIS IS A MEDICAL CONDITION CAUSED BY AN EXCESSIVE AMOUNT OF
THYROID HORMONES IN THE BLOODSTREAM.
• THE TERM THYROTOXICOSIS IS SOMETIMES INTERCHANGED WITH HYPERTHYROIDISM
THOUGH THEIR DEFINITIONS ARE SLIGHTLY DIFFERENT.
• THE CLINICAL EFFECTS EXPERIENCED DUE TO AN EXCESS OF THYROID HORMONES IN THE
BLOODSTREAM. HORMONES PRODUCED BY THE THYROID GLAND CONTROL HOW FAST OR
SLOW THE BODY WORKS (METABOLIC RATE). TOO MUCH THYROID HORMONE (THYROXINE
AND TRIIODOTHYRONINE) SPEEDS UP THE METABOLISM AND RESULTS IN THE SIGNS AND
SYMPTOMS OF THYROTOXICOSIS.

3. WHAT CAUSES THYROTOXICOSIS?
• THE MAIN CAUSE OF THYROTOXICOSIS IS HYPERTHYROIDISM, WHICH IS AN OVERACTIVITY OF
THE THYROID GLAND RESULTING IN IT PRODUCING EXCESS LEVELS OF THYROID HORMONES.
• IF THE HYPERTHYROIDISM IS DUE TO AN AUTOIMMUNE CAUSE, IT IS CALLED GRAVES'
DISEASE.
• OTHER RARER CAUSES OF THYROTOXICOSIS INCLUDE EXCESSIVE INTAKE OF THYROID
HORMONE IN PATIENTS TREATED FOR HYPOTHYROIDISM (AN UNDERACTIVE THYROID GLAND)
AND SOMETIMES, INFLAMMATION OF THE THYROID GLAND (THYROIDITIS), WHICH CAUSES
RELEASE OF LARGE QUANTITIES OF THYROID HORMONE INTO THE BLOODSTREAM.

4. WHAT ARE THE SYMPTOMS OF THYROTOXICOSIS?
• THE SYMPTOMS OF THYROTOXICOSIS ARE A RESULT OF THE HIGH LEVELS OF
THYROID HORMONES IN THE BLOOD, INCREASING THE METABOLIC RATE.
• THESE CAN INCLUDE DIARRHEA, WEIGHT LOSS, SHAKING OR TREMOR (NOTABLY IN
THE HANDS), SWEATING, INCREASED HEART RATE THAT CAN BE FELT BY THE PATIENT
(PALPITATIONS), OVERACTIVITY, AGITATION, ANXIETY, CHANGES IN EMOTIONS AND
FEELING HOT EVEN THOUGH THE ROOM MAY FEEL COLD TO EVERYONE ELSE.
PATIENTS MAY ALSO EXPERIENCE AN INCREASED HEART RATE, THINNING OF THE
HAIR, SWELLINGS OR NODULES IN THE THYROID GLAND (GOITRE).

5. HOW IS THYROTOXICOSIS DIFFERENT FROM THYROID STORM?
• THYROID STORM, ALSO REFERRED TO AS THYROTOXIC CRISIS, IS AN ACUTE, LIFE-THREATENING,
HYPERMETABOLIC STATE INDUCED BY EXCESSIVE RELEASE OF THYROID HORMONES (THS) IN INDIVIDUALS
WITH THYROTOXICOSIS.
• THYROID STORM MAY BE THE INITIAL PRESENTATION OF THYROTOXICOSIS IN UNDIAGNOSED CHILDREN,
PARTICULARLY IN NEONATES.
• THE CLINICAL PRESENTATION INCLUDES FEVER, TACHYCARDIA, HYPERTENSION, AND NEUROLOGICAL AND
GI ABNORMALITIES. HYPERTENSION MAY BE FOLLOWED BY CONGESTIVE HEART FAILURE THAT IS
ASSOCIATED WITH HYPOTENSION AND SHOCK.
• BECAUSE THYROID STORM IS ALMOST INVARIABLY FATAL IF LEFT UNTREATED, RAPID DIAGNOSIS AND
AGGRESSIVE TREATMENT ARE CRITICAL. FORTUNATELY, THIS CONDITION IS EXTREMELY RARE IN CHILDREN.
• DIAGNOSIS IS PRIMARILY CLINICAL, AND NO SPECIFIC LABORATORY TESTS ARE AVAILABLE. SEVERAL
FACTORS MAY PRECIPITATE THE PROGRESSION OF THYROTOXICOSIS TO THYROID STORM

6. HOW DO YOU DIFFERENTIATE BETWEEN NEW ONSET THYROID
DISEASE AND EXOGENOUS THYROID INGESTION/MISUSE?
• PATIENTS WITH THYROTOXICOSIS AND HIGH LEVELS OF T3 AND T4
WITH SUPPRESSED TSH AND LOW LEVELS OF THYROID-BINDING
GLOBULIN ARE LIKELY TO HAVE SYMPTOMS RELATED TO EXOGENOUS
THYROID HORMONE INGESTION/MISUSE.

7. ARE THERE ANY SIMILARITIES BETWEEN THYROID MEDICATION AND
LITHIUM OVERDOSE?
• GI SYMPTOMS MAY BE SEEN IN BOTH (NAUSEA, VOMITING, DIARRHEA)
• COURSE TREMOR IS A PROMINENT FINDING OF LITHIUM TOXICITY
WHILE A FINE TREMOR IS MORE TYPICAL OF THYROID HORMONE EXCESS.
• NEUROLOGIC FINDINGS SUCH AS ALTERED MENTAL STATUS, COMA, AND SEIZURES ARE SEEN
WITHIN 1–2 DAYS AFTER AN ACUTE LITHIUM OVERDOSE OR AS A LATE FEATURE OF CHRONIC
EXCESS.
• -CARDIAC CONDUCTION ABNORMALITIES ARE MORE TYPICAL OF LITHIUM THAN THYROID
HORMONE OVERDOSE; TACHYCARDIA MAY BE SEEN IN BOTH, BUT WOULD BE MORE PRONOUNCED
AND ASSOCIATED WITH OTHER SYMPATHOMIMETIC SYMPTOMS IN THYROID EXCESS .

8. IS ACTIVATED CHARCOAL AN OPTION TO PREVENT DRUG
ABSORPTION WITH THYROID HORMONE INGESTIONS?
• ACTIVATED CHARCOAL IS AN OPTION FOR THYROID HORMONE INGESTIONS AND CAN BE GIVEN
WITHIN 1 H FROM TIME OF INGESTION FOR MAXIMAL EFFECT.
• THYROID HORMONE BINDS TO ACTIVATED CHARCOAL.
• IT IS EASY TO REACH A 10:1 RATIO OF ACTIVATED CHARCOAL: THYROID HORMONE INGESTED DUE
TO MCG SIZED TABLETS
• THERE ARE VARYING RECOMMENDATIONS FOR THE ADMINISTRATION OF ACTIVATED CHARCOAL FOR
THYROID HORMONE INGESTIONS. ONE EXAMPLE IS AS FOLLOWS:
• AGE > 12 MONTHS AND
• THYROID HORMONE INGESTION >3 MG SHOULD RECEIVE <3 MG INGESTIONS SHOULD NOT NEED
AS LOW LIKELIHOOD OF DELAYED SYMPTOMS

9. WHAT IS THE GENERAL TIME FRAME FROM INGESTION OF
LEVOTHYROXINE (T4) TO DEVELOPMENT OF SYMPTOMS?
• THE ONSET OF SYMPTOMS AND SIGNS MAY BE DELAYED FOR UP TO 3 TO 10 DAYS.
• MEDICAL CONSENSUS HAS INDICATED THAT SERIOUS SYMPTOMS ARE LESS FREQUENT IN CHILDREN EVEN
THOUGH CHILDREN USUALLY HAVE HIGHER MEAN PLASMA LEVELS OF T4 AND T3 THAN ADULTS FOR THE
SAME OVERDOSE OF LT4 INGESTED.
• AS ALREADY MENTIONED SERIOUS COMPLICATIONS ARE NOT COMMON, BUT THEY CAN APPEAR DAYS
AFTER INGESTION, AND THEREFORE THE PATIENTS SHOULD BE CLOSELY MONITORED.
• PATIENTS THAT HAVE INGESTEDT3 CONTAINING PRODUCTS MAY DEVELOP SOME SYMPTOMS WITHIN
HOURS

10. IS THERE ANY ROLE FOR EARLY LABORATORY EVALUATION
OF ACUTE LEVOTHYROXINE (T4) OR T3 INGESTIONS?
• ALTHOUGH T4 IS RABIDLY ABSORBED FROM GIT WITHIN THE FIRST (1-2) HOURS
WHICH CAUSES A RISE IN SERUM T4,THERE IS A NEGATIVE FEEDBACK MECHANISM
WHICH LIMITS ITS CONVERSION TO T3 (TRIIODOTHYRONINE).
• SO T4 MEASUREMENT DO NOT CORRELATE WITH SYMPTOMOS
• IT MIGHT BE HELPFUL ONLY TO ASSURE THE INGESTION OF T4

11. WHAT IS THE STANDARD TREATMENT FOR CHRONIC OR ACUTE
INGESTION OF THYROID HORMONE RESULTING IN THYROTOXICOSIS?
• SUPPORTIVE CARE.
• IV FLUIDS.
• BENZODIAZEPINES FOR AGITATION OR ANXIETY (ANTIPSYCHOTICS MAY WORSEN CONDITION).
• ACTIVE COOLING, BENZODIAZEPINES, AND POSSIBLY INTUBATION FOR HYPERTHERMIA.
• BETA-BLOCKERS (TYPICALLY PROPRANOLOL) FOR TACHYCARDIA.
• ACETAMINOPHEN FOR FEVER CAN BE CONSIDERED IF DIAGNOSIS IN DOUBT, HOWEVER WOULD NOT
BE EFFECTIVE FOR THYROTOXICOSIS.

12. WHY DON’T WE USE OTHER MEDICATIONS TYPICALLY USED TO
TREAT NATURALLY OCCURRING THYROTOXICOSIS TO TREAT
OVERDOSES?
• THE SYMPTOM COURSE IS TYPICALLY SHORT AND RESOLVES WITH ONGOING
ELIMINATION OF ACTIVE THYROID HORMONE; NEGATIVE FEEDBACK IS NORMALLY
OPERATIVE, RESULTING IN CESSATION OF ENDOGENOUS THYROID HORMONE RELEASE.
• IN ADDITION, CONVERSION OF T4 TO “REVERSET3” (RT3) CAN MINIMIZE SOME
OF THE EFFECTS OF T3 AS RT3 BINDS TO THYROID RECEPTORS BUT DOES NOTACTIVATE THEM

13. WHY IS USE OF PROPRANOLOL BENEFICIAL ?
• PROPRANOLOL IS THE PREFERRED AGENT FOR Β-BLOCKADE IN HYPERTHYROIDISM AND THYROID STORM
DUE TO HYPERTHYROIDISM IS ASSOCIATED WITH AN INCREASED NUMBER OF BETA-ADRENERGIC
RECEPTORS . THE ENSUING INCREASE IN BETA-ADRENERGIC ACTIVITY IS RESPONSIBLE FOR MANY OF THE
SYMPTOMS ASSOCIATED WITH THIS DISORDER.
• IT ALSO EXPLAINS THE ABILITY OF BETA BLOCKERS TO AMELIORATE RAPIDLY MANY OF THE SYMPTOMS,
INCLUDING PALPITATIONS, TREMBLING, AND ANXIETY ARE MEDIATED BY INCREASES IN BETA-ADRENERGIC
RECEPTORS ON CELL SURFACES.
• BETA BLOCKERS, TYPICALLY USED TO TREAT HIGH BLOOD PRESSURE, ARE A CLASS OF DRUGS THAT OFFSET
THIS EFFECT,RANDOMIZED TRIAL, PATIENTS RECEIVING BETA BLOCKERS WITH METHIMAZOLE,COMPARED
WITH PATIENTS RECEIVING METHIMAZOLE ALONE, HAD A LOWER HEART RATE AND IMPROVEMENT IN
FATIGABILITY, SHORTNESS OF BREATH, AND PHYSICAL FUNCTIONING AFTER FOUR WEEKS OF THERAPY. ITS
ADDITIONAL EFFECT OF BLOCKING THE PERIPHERAL CONVERSION OF INACTIVE T4 TO ACTIVE FORM T3 BY
INHIBITION OF THE 5'-MONODEIODINASEPROPRANOLOL IS HIGHLY LIPID SOLUBLE, ALLOWING IT TO
BECOME SUFFICIENTLY CONCENTRATED IN TISSUES TO INHIBIT MONODEIODINASE ACTIVITY.NOTE :- THAT
THESE DRUGS DO NOT TREAT HYPERTHYROIDISM OR ANY OF ITS LONG-TERM EFFECTS IF LEFT UNTREATED,
BUT, RATHER, THEY TREAT OR REDUCE ONLY SYMPTOMS OF THE CONDITION.

14. WHAT CAN YOU USE IF A BETA-BLOCKER IS
CONTRAINDICATED (I.E., THE PATIENT IS ASTHMATIC)?
• TREATMENT OF ASTHMA ( TOPICAL TREATMENT ) :- INHALED BRONCHODILATOR MEDICATIONS AS
SHORT-ACTING Β-AGONISTS, SUCH AS SALBUTAMOL,INHALED ANTICHOLINERGICS ARE
TIOTROPIUM (SPIRIVA) AND IPRATROPIUM BROMIDE.
• RADIOACTIVE IODINE IN IODINE-131 (RADIOIODINE) RADIOISOTOPE THERAPY IS GIVEN ORALLY
(EITHER BY PILL OR LIQUID) ON A ONE-TIME BASIS, TO SEVERELY RESTRICT, OR ALTOGETHER
DESTROY THE FUNCTION OF A HYPERACTIVE THYROID GLAND.
• THIS ISOTOPE OF RADIOACTIVE IODINE USED FOR ABLATIVE TREATMENT IS MORE POTENT THAN
DIAGNOSTIC RADIOIODINE SURGERY NOT EXTENSIVELY USED BECAUSE MOST COMMON FORMS
OF HYPERTHYROIDISM ARE QUITE EFFECTIVELY TREATED BY THE RADIOACTIVE IODINE METHOD,
AND BECAUSE THERE IS A RISK OF ALSO REMOVING THE PARATHYROID GLANDS, AND OF
CUTTING THE RECURRENT LARYNGEAL NERVE

15. WHAT ARE SIDE EFFECTS OF PROPRANOLOL USE IN
CHILDREN SHOULD PROVIDERS BE AWARE OF?
• HYPOGLYCEMIA
• THIS IS A DIRECT EFFECT OF THE PROPRANOLOL (LOSS OF BETA-RECEPTOR-MEDIATED
GLYCOGENOLYSIS, LIPOLYSIS, AND GLUCONEOGENESIS) AND MAY BE EXACERBATED BY DECREASED
ORAL INTAKE WHILE IN HOSPITAL SETTING
• BRADYCARDIA.

16. HOW IS DISPOSITION DETERMINED AFTER AN INGESTION
OF THYROID MEDICATION?
• ACCIDENTAL INGESTIONS OF T4 CONTAINING AGENTS IN OTHERWISE HEALTHY PATIENTS WITH
RELIABLE ACCESS TO HEALTH CARE CAN BE SENT HOME WITH STRICT RETURN PRECAUTIONS
• IF A PATIENT ARRIVES LESS THAN AN HOUR AFTER ISOLATED LEVOTHYROXINE INGESTION, IT IS
REASONABLE TO GIVE THEM ACTIVATED CHARCOAL AND DISCHARGE THEM HOME.
• THIS GUIDANCE ALSO APPLIES TO PATIENTS ON THYROID MEDICATION CHRONICALLY WITH AN
ACUTE ACCIDENTAL OR INTENTIONAL OVERDOSE

17. HOW DO YOU FOLLOW THESE PATIENTS IN THE HOSPITAL
AND AFTER DISCHARGE TO ENSURE IMPROVEMENT?
• THERE IS NO NEED FOR FREQUENT T4 TESTING ONCE A DECREASING TREND IS
DOCUMENTED
• FREE T3 LEVELS IS A BETTER WAY OF DETERMINING IMPROVEMENT
• ASSESSING THE IMPACT OF PROPRANOLOL THERAPY.
• NO NEED FOR FREQUENT T4 TESTING ONCE A DECREASING TREND IS DOCUMENTED.
• SYMPTOMS SHOULD BE SUBSIDING AND TREATMENT CAN BE DISCONTINUED.

18. THANK
YOU