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