Download - Thyroid
ENDOCRINOLOGY
K.M.LAKSHMANARAJAN
THYROID
REF FROM API –SIDDARTH N SHAH
• One of the earliest gland to develop• Thyroid follicular cells acquire capacity to form
thyroglobulin (tg) by 29 th day of gestation• Ability to counteract to concentrate iodine – 11th
week of gestation • TBG detectable at 10 th week • RT lobe more vascular than LT lobe • 15-20 gm ,4 cm ht
BLOOD SUPPLY
• Superior thyroid artery –external carotid artery• Inferior thyroid artery-thyrocervical trunk • Thyroidia ima- brachiocephalic artery
THYROXINE SYNTHESIS
• IODIDE TRAPPING-NAI SYMPOTER
• OXIDATION – TPO
• ORGANIFICATION
• COUPLING -TPO
SYNTHESIS
• Acute uptake of iodine by Na I symporter (NIS)• NIS-643 aminoacids protein • NIS also expressed in breast,salivary gland also • Pendrin –iodine transport • Expressed by PDS gene
• Mutations in NIS/PDS gene→ congenital hypothyroidism
IODINE – OXIDISED BY TPO
↓
IODINATION OF THYROSINE MOLECULES IN TG
↓
ORGANIFICATION
COUPLING MECHANISM BY TPO
• Thyroid gland –store hormone to maintain euthyroid state for 6-8 weeks
• TSH –formation,release of thyroid hormones
conversion of T4-T3• TSH suppressors-somatostatin ,steroids,IL1,
TNF α,phenytoin,dopamine
• TSH,TRH –SUPPRESSED BY T4
• T4-T3 conversion impaired by fasting ,acute trauma,oral contrast agents, propylthiouracil , propronolol, amiadarone, steroids
• 75-80 % - bound to TBG• Also to trans thyretin (t4 binding pre albumin)• Unbound form –enters cells - biological effects
by inding to nuclear DNA bund receptors • T3 – 15 fold binding affinity than t4
• T4/T3 ratio= 10/1
• Daily secretion of t4- 80-100 ug
• T ½ of t4 – 7-8 days
• T1/2 of t3 – 3 days
• RDA OF IODINE -150 UG /DAY –NON PREG
• 200 UG-PREG
TFT
TSH 0.4-5.0 MU/L
T4-TOTAL 5.0-12.0 UG/DL
T4 FREE 0.9-2.4 NG/DL
T3 70-195 NG /DL
FREE THYROXINE
INDEX (T4*RT3U)
1.2-4.9
T3 UPTAKE 24-39%
REVERSE T3
• rT3 is the iinactive form of T3• Derived from T4 by deiodinase enzyme• It accounts for 10%• In stress , critically ill pateints, steroids therapy,
wilsons disease rT3 level increased and occypy T3 receptors
• So normal T3 will bind less and patient may have hypothyroid features
TSH
• 0.1-0.4 – SUBCLINICAL HYPERTHYROIDISM
• <0.03 – OVERT HYPERTHYROIDISM • <0.01-THYROID STORM
• 5-10 WITH NORMAL FT4,FT3-SUBCLINICAL HYPOTHYROIDISM
• >20MU/L-OVERT HYPOTHYROIDISM
THYROID BINDING GLOBULIN
INCREASED IN DECREASED IN
OCPSPREGNANCYESTROGENSHEPATITISNEONATES
ACUTE INTERMITTENT
PRPHYRIAINHERITED
CONDITIONS
TESTOSTERONESTEROIDS
SEVERE ILNESSCIRRHOSISNEPHROTIC SYNDROMEINHERITED DISORDER
TRH STIMULATION TEST
• For testing hypothalamo pituitary axis • IV TRH 200 ug shows rise of in serum tsh level
in 20 mins (from basal 1 u unit /ml to 10 u unit /ml)
• Reaches normal in 2 hrs • In hyperthyroidism –no response • Hypothyroid-over response• HPA problem-subnormal response
THYROID-HYPERTHYROIDISM
• Excess stimulation of thyroid follicles by thyrotropin or
• By autoantibodies to thyroid peroxidase →bind to thyrotropin binding sites
CAUSES OF HYPERTHYROIDISM
• GRAVES DISEASE
• MNG
• THYROID STORM
• JODBASEDOW PHENOMENON
• THYROIDITIS-HASIMOTOS
• PREGNANCY
• THYROID AUTONOMOUS ADENOMA
• FACTITIOUS HYPERTHYROIDISM
THYROTOXICOSIS
• Wt loss,incresed appetite – due to increased BMR
• Hyperactivity ,nervousness, irritability
• Sense of easy fatiguability,
• Insomnia,impaired concentration,
• Fine tremor,hyper reflexia,muscle rigidity
• Proximal myopathy with out fasciculation,
• chorea –rare
• Appathetic thyrotoxicosis-elderly pts present fatigue and wt loss
• Features of throtoxicosis may be subtle or masked
GRAVES DISEASE - EYE
• LID RETRACTION AND PROPTOSIS
• RETRO BULBAR SWELLING
• EXOPHTHALMOUS PRODUCING SUBSTANCE –FROM ANTERIOR PITUITARY
• LATS
• DIPLOMIA & OEDEMA OF CONJUCTIVA
• MALIGNANT EXOPHTHALMOS
CVS
• Sinus tachycardia –persistent during sleep• Arrhythmias –extra systole,atrial fibrillation• Systolic pressure increased• CCF• Systolic hypertension
• CVS –sinus tachycardia ,palpitations
svt
Bounding pulse ,widened pulse pressure
aortic systolic murmur • SKIN –warm ,moist ,heat intolerance
palmar erythema ,onycholysis ,pruritus,
Urticaria
Diffuse alopecia• GIT-diarrhea• Bone –osteopenia ,mild
hypercalcemia,hypercalciuria
RS
• VITAL CAPACITY REDUCED
• Increased BMR• Insulin turnover aggaravated• Lipogenesis,lipolysis increased• TG decreased• Sympathetic system-no increase in
catecholamines• Increase catecholamine sensitivity & beta
receptors • T3 act directly on myocyte9over expression of
type 2 deiodinase in heart
• BMR is increased 80-90%• Glycosuria• Fine tremors
• MECHANICAL EFFECTS • Recurrent laryngeal nerve• Hoaseness of voice• Dysphagia• dyspnoea
TREMORS
• FINE TREMORS IN OUTSTRETCHED HANDS
• TONGUE WITH IN ORAL CAVITY
EYE SIGNS
• Vongraefe’s sign- lid lag sign visible –upper sclera visible
• Naffziger’s sign –eyeball seen beyond superior orbital margin
• Dalrymple’s sign –upper lid retraction,visibility of upper sclera
• Stellwag’s sign –absence of normal blinking –staring look-first sign to appear
• Joffroy’s sign –absence of wrinkling in forehead • Moebius sign –lack of convergence of eyeball –due to
lymphocytic infiltration of inferior oblique muscle
• Jellineks sign –increase pigmentation of eyelid margins
• Enroth sign –edema of eyelids • Rosenbach sign -tremor of closed eyelids • Trousseau’s sign –dislocation of eye globe
REPRODUCTIVE SYMPTOMS
• Irregular periods• Anovulatory cycle • Fertility reduced• Miscarriages• The increased rate of conversion of androgens to
estrogenic by-products -gynecomastia and erectile dysfunction in men
• for menstrual irregularities in women.• Disruption in amplitude and frequency of lh/fsh
pulses due to thyroid hormone influences on GNRH signaling.
SKIN
• THYROID DERMOPATHY –PRETIBIAL EDEMA
• THYROID ACROPACHY LIKE CLUBBING
HYPERTHYROIDISM –EVALUATION
MEASURE T4,TSH
HIGHT4,LOW TSH
NT4,LOWTSH
N T 4,N TSH
HIGHT4,N TSH
HIGHT4,HIGH TSH
I°thyrotoxicosis
MEASURE FT3 EUTHYROID
Thyrotropinoma,hormone resistance,autoantibodies to t4,drugs
HIGH NORMAL
T3 THYROTOXICOSIS EUTHYROID
GRADING OF HYPERTHYROIDISM
• NO SPECS CLASSIFICAATION • N- NO EYE SYMPTOMS,SIGNS• O-OMLY SIGNS, NO SYMPTOMS
(LID RETRACTION,STERE LOOK,LID LAG,PROPTOSIS
• S-SOFT TISSUE INVOLVEMENT• P-PROPTOSIS >22 MM• E-EXTRA OCULAR MUSCLES • C-CORNEAL INVOLVEMENT• S-SIGHT LOSS (OPTIC NERVE INVOLVEMENT)
TREATMENT OF HYPERTHYROIDISM
• Methimazole ,carbimazole ,propylthiouracil
- inhibit thyroid hormone sysynthesis
PTU-inhibits extrathyroidal conversion t4-t3
Carbimazole –converted into methimazole
30 -45 mg/day in tds
PTU -50 to 100 mg 8n th hrly
• BLOCK REPLACEMENT REGIMEN • Large dose of carbimazole to totally block
thyroid hormone
↓
Thyroxine supplement to maintain euthyroid regimen
Lugols iodine – 3-5 drops tid
SSKI-one drop tid
TREATMENT OF HYPERTHYROIDISM
• RADIO ACTIVE I 131
simple ,effective , economical
8500 rad
Remissions
Hypothyroidism
• PROPRONOLOL,IODINE –SHRINKS THE GLAND
• 7-14 DAYS
DRUGS
• Antithyroid drugs • Carbimazole more potent • Less protein bound• 12-24 hrs duration action • Metabolite –methimazole• PTU • 4-8 hrs duration• Less potent • Highly plama protein bound• Less placenta crossing • Inhibit peripheral t4-t3 conversion
IODIDE TRAPPING INHIBITORS
• SCN• PERCLORATES
IODINES /IODIDES
• LUGOLS IODINE -5% IODINE +10%POTASSIUM IODIDE
• SSKI• SODIUM IODIDE• IOPONIC ACID• IOPDATE• DECREASE VASCULARITY• DECREASE HORMONE RELEASE• SHRINKS THE GLAND
IODIDES/IODINE
• Thyroid constipation • Inhibition of thyroid hormone by iodine/iodide-
thyroid constipation • Endocytosis of colloid/proteolysis of
thyroglobulin-halted
• Wolf chaikoff effect• Excess iodide inhibits its own transport in to
thyroid cells & alter redox potencial of cells-reduced t3/t4 synthesis
RADIO IODINE
• Contra indicated in pregnancy and pediatrics
• IODIDES - ↓THYROID SECRETION
• ↓THYROID GLAND VASCULARITY
THYROID STORM
• Tachycardia ,hypertension• Highoutput CCF,• Fever• Anxiety,nausea,vomiting,diarrhea• Causes
Thyroidal & non thyroidal surgery
Delivery ,sepsis,trauma
Iodine,iodide,amiadarone
Burns
• Burns –marked hypoprotenemia
↓
high circulating thyroid hormones
TREATMENT OF THYROID STORM
• PTU – 600 MG loading ,200-300 mg 6 th hrly PO/ryle tube
• 1 hr after – iodide – to block thyroid synthesis (wolff chaikoff effect)
• The delay allows the antithyroid drug to prevent the excess iodine from being incorporated with new hormone
• Sski-5 drops 6 th hrly • Ipodate ,iopanic acid -0.5 mg every 12 hrly• Sodium iodide -0.25 mg iv 6 hrly • Propronolol -40 -60 mg orally 4 th hrly
IV 2 mg 4 thy hrly
• DEXAMETHASONE 2 MG 6THY HRLY • COOLING • OXYGEN • IVF
TREATMENT OF THYROTOXICOSIS CRISIS
• Dantrolene (for any metabolic crisis)• Beta blockers• NTG,labetalol,SNP• Steroids,iodides,antithyroid drugs• Benzodiazepines• Ionotropes-phosphodiasteraseinhibitor to ↑
FOC,with out ↑ HR• Plasma exchange at last • Dialysis,charcoal hemoinfiltration
THYROID –PREGNANCY
• Transient increase in Hcg –1 st TM –stimulates TSH –R
• Estrogen induced rise in TBG 1 st TM –sustained during preg
• Alteration in immune system –onset exacerbation or amelioration of underlying autoimmune thyroid disease
• Increased thyroid hormone metabolism by placenta
• Increased urinary iodide excreation
HYPERTHYROIDISM IN PREGNANCY
• If not controlled may lead to thyroid storm,toxemia,premature delivery,abruptio placenta,ccf,thyroid crisis
AMIADARONE & THYROID
• Structurally related to thyroid hormone
• 39 % iodine content
• Amiadarone –stored in adipose tissue –persist > 6 months even after discontinuation of drug
• It inhibits deoidinase activity
• Metabolite function as weak antagonists of thyroid hormone
AMIADARONE & THYROID
• 1. Acute transient suppression of thyroid function • 2.Hypothyroidism in pts susceptible to inhibits
effects of high iodine load • 3.Thyrotoxicosis –by jod-basedow effect
• Amiadarone induced thyrotoxicosis • -in underlying thyroid abnormality • Jod base dow effect• Drug induced lysosomal activation –destructive
thyroiditis
TREATMENT OF AMIADARONE THYROTOXICOSIS
• Discontinuation of amiadarone • Sodium ipodate 500 mg/day • Sodium tyropanoate 500 mg 1-2 dose /day
decrease t4 –t3 conversion
Potassium perchloarte 200 mg 6 th hrly
Steroids
Lithium –modest benefit
PRE OP PREPARATION
• INVESTIGATION
• HB-ANEMIA,REDUCED INTRAVASCULAR VOLUME
• TC.DC.ESR-INFECTION.THYROIDITIS
• TFT
• X RAY NECK/CT NECK-TRACHEAL COMPRESSION,RETROSTERNAL GOITRE
• UREA,CREATININE
• ECG-AF
• ECHO
PREMED
• BENZODIAZEPINES,NARCOTICS,CLONIDINE
• AVOID ATROPINE
INDUCTION
• Thoipental – thiouylene nucleus- decrease t4-t3 conversion
• Suxa-IF DIFFICULT INTUBATION • Vecuronium,rocuronium-cvs STABILITY• Eye protection-proptosis • Phenyl ephrine –VASOPRESSORS WITHOU
INCRESING HR
MAINTENENCE
• ISO ,SEVOFLURANE ,DESFLURANE • AVOID ATRACURIUM • FENTANYL,REMIFENTANIL• AVOID MORPHINE,PETHIDINE
MONITORING
• ROUTINE• ETCO2• ECG-MUST
• CVP• IABP• URINE OUPUT• TEMPRATURE-MUST
REVERSAL
• NEOSTIGMINE• GLYCOPYRROLATE• STRESS ATTENUATION
• Avoid adrenaline for local infiltration
SLEEPING PULSE CHART
• At late night or in early morning for 3 consecutive days –average
• Avoid sedation • Crile’s grading
CRILES GRADING SLEEPING PULSE /MIN
I UPTO 90
II 90-110
III 110
POST OPERATIVE COMPLICATIONS
• BLEEDING• HEMATOMA & AIRWAY OBSTRUCTION • VOCAL CORD PALSY • HYPOCALCEMIA& TETANY
HEMATOMA
• Immediate wound exploration • Intubation may be difficult• Awake intubation • Remove the suture even in the ward itself • Blood transfusion
VOCAL CORD PALSY
• Common is recurrent nerve palsy • Abductor fibres more vulnerable to trauma • Severe or section of nerve only produce both
abductors and adductors palsy • Unilateral pure abductor palsy –no problem • Unilateral both abductors and adductors-
hoarseness,aspiration • Bilateral partial (abductors )-stridor/aphonia• Bilateral complete – aphonia • But respiration affected in high effort
TOTAL PALSY
• Cadaveric position • Intubation position
SLN PALSY
• Husky voice• Topical application of local anesthetic sometime
can cause sln paresis –husky voice
HYPOCALCEMIA• Normal – 8.6- 10.4 mg/dl
• O.8 mg /dl fall with fall in 1 gm /dl of albumin
• Signs of hypocalcemia
• Chovsteck’s sign
• Trousseau sign
• Tetany at 7- 8 mg/dl
• Calcium chloride (10%): 100 mg per ml
Contains 27.2 mg/ml elemental calciuum
Preferred calcium preparation
• Calcium gluconate (10%)
contains 9 mg/ml elemental calcium
• Calcium gluceptate
• DOSING: CALCIUM GLUCONATE 10%
HYPOCALCEMIA • CALCIUM GLUCONATE 1 GRAM IN 50
ML D5W OVER 1 HOUR
EMERGENT DOSING • INITIAL: 2 AMPULES (20 ML) IV OVER
10-30 MINUTES• MAINTENANCE: 60ML IN 500ML D5W
AT 0.5-2.0 MG/KG/H
• DOSING: CALCIUM CHLORIDE (10%)
GENERAL INDICATIONS (E.G. HYPERKALEMIA) • CHILD: 0.2 - 0.25 ML/KG GIVEN VERY
SLOWLY• ADULT: 8 - 16 MG/KG GIVEN VERY
SLOWLY
PROPHYLAXIS OF CALCIUM CHANNEL BLOCKER HYPOTENSION • INITIAL: 2 - 4 MG/KG IV GIVEN VERY
SLOWLY• REPEAT AS NEEDED EVERY 10 MINUTES
MEN SYNDROME
• MEN 1 (wermer syndrome)
• Parathyroid
• Pancreatic islet cell tumor
• Pituitary adenoma
• MEN 2 A
• Parathyroid adenoma
• medullary carcinoma thyroid
• Pheochromocytoma
• MEN 2B
• MCT
• PHEOCHROMOCYTOMA
• GI&MUCOSAL NEUROMAS
LEAK TEST
• Tracheomalacia • Racheomalacia is a condition characterized by
flaccidity of the tracheal support cartilage which leads to tracheal collapse especially when increased airflow is demanded-expiratory stridor
• Wolff–Chaikoff effect is hypothyroidism caused by ingestion of a large amount of iodine
• The Jod-Basedow phenomenon is iodine-induced hyperthyroidism.
RETROSTERNAL GOITRE
• Dyspnea in lying • Hoarseness of voice in lying• tracheal compression may be there • Kocher’s test –clinically• Pembertson’s sign • Ct chest
• Median sternotomy may need to excise
TRACHEAL COMPRESSION
• Kocher’s method –pt asked to see straight
• With fingers of and thumb , both lateral lobes of thyroid gland are gently compressed –posteromedially
• If pt have stridor –test is positive
•
REVERSAL CRITERIA
TIDAL VOLUME 5 ML/KG 80 % RECOVERY
SINGLE TWITCH 75-80
TOF NO FADING 70-75%
VITAL CAPACITY
20ML/KG 70%
BOUBLE BURST NO FADE 50%
INSPIRATORY FORCE
_40 CMH20 50%
HEAD LIFT FROM 180 DEG SUPINE – 5 SEC
50%
HAND GRIP 50%
SUSTAINED BITE JAW CLENCH ON TONGUE BLADE
50%
Diagnostic criteria for thyroid storm (adapted from Burch and Wartofsky5)
Thermoregulatory dysfunction
Temperature (°F)
99–99.9 5
100–100.9 10
101–101.9 15
102–102.9 20
103–103.9 25
≥104.0 30
Cardiovascular dysfunction
Tachycardia (bpm)
90–109 5
110–119 10
120–129 15
130–139 20
≥140 25
Congestive heart failure
Absent 0
Mild-pedal oedema 5
Moderate-bibasilar rales 10
Severe-pulmonary oedema 15
Atrial fibrillation
Absent 0
Present 10
Central nervous system effects
Absent 0
Mild 10
Agitation
Moderate 20
Delirium
Psychosis
Extreme lethargy
Severe 30
Seizure
Coma
Gastrointestinal–hepatic dysfunction
Absent 0
Moderate 10
Diarrhea
Nausea/vomiting
Abdominal pain
Severe 20
Unexplained jaundice
Precipitant history
Negative 0
Positive 10