Post Partum Shakes:Post Partum Shakes: A Case of PPT With a TwistA Case of PPT With a Twist

Sanam Shorey M.D. Sanam Shorey M.D.

Endocrinology FellowEndocrinology Fellow

March 5, 2003March 5, 2003

OUTLINEOUTLINE

Case PresentationCase Presentation Definition, Prevalence Definition, Prevalence Pathophysiology Pathophysiology Predisposing FactorsPredisposing Factors Diagnosis and Treatment, Follow-up, Morbidities? Diagnosis and Treatment, Follow-up, Morbidities? Current Screening Recommendations?Current Screening Recommendations? PPTD and Depression Linked??PPTD and Depression Linked?? Revisit the CaseRevisit the Case

CASECASE

28yo G1P1A0L128yo G1P1A0L1 2 months post partum 2 months post partum C/O fatigue, irritability, sweats, heat intoleranceC/O fatigue, irritability, sweats, heat intolerance No hx preceding illness, neck pain, or eye No hx preceding illness, neck pain, or eye

changeschanges No Personal hx Thyroid or DiabetesNo Personal hx Thyroid or Diabetes No Family hx Thyroid or DiabetesNo Family hx Thyroid or Diabetes Medns: NilMedns: Nil Allergies: NilAllergies: Nil

CASE (cont’d)CASE (cont’d)

BP 100/62, HR: 72bpm regularBP 100/62, HR: 72bpm regular

TG: palpable, firm at 25 grams, no nodularity TG: palpable, firm at 25 grams, no nodularity or audible bruitsor audible bruits

Mild infraorbital puffiness without proptosis Mild infraorbital puffiness without proptosis or lid lagor lid lag

Brisk reflexesBrisk reflexes

CASE (cont’d)CASE (cont’d)

TFTS: FT4 20, TSH <0.05TFTS: FT4 20, TSH <0.05

A-MC 1:25600A-MC 1:25600

TBII negativeTBII negative

Thyroid Scan and Uptake: Low RAIUThyroid Scan and Uptake: Low RAIU

CASE (cont’d)CASE (cont’d)

Dx: Post partum thyrotoxicosisDx: Post partum thyrotoxicosis

Not symptomatic enough to warrant Not symptomatic enough to warrant propranololpropranolol

TFTs q monthly TFTs q monthly euthyroid in 2-3 months euthyroid in 2-3 months

Warned about impending hypothyroidismWarned about impending hypothyroidism

CASE (cont’d)CASE (cont’d)

Presented 6 months post partumPresented 6 months post partum

C/O intermittent fatigue, occasional C/O intermittent fatigue, occasional confusion, moderate weight gainconfusion, moderate weight gain

O/E: O/E:

BP 110/70, HR 72 BP 110/70, HR 72

TG normal size with no nodularityTG normal size with no nodularity

Achilles reflex delayed relaxationAchilles reflex delayed relaxation

CASE (cont’d)CASE (cont’d) TSH 18TSH 18 FT4 (low)FT4 (low) A-MC: positive 1:6400A-MC: positive 1:6400

Confirmed resolution of thyrotoxicosis and Confirmed resolution of thyrotoxicosis and development of hypothyroidism (typical or development of hypothyroidism (typical or biphasic PPT)biphasic PPT)

L-T4 commenced and pt restored to L-T4 commenced and pt restored to euthyroidism 9 months postpartum euthyroidism 9 months postpartum

L-T4 d/c 14 months after deliveryL-T4 d/c 14 months after delivery F/U TFTs q 6 monthsF/U TFTs q 6 months

POST PARTUM THYROIDITISPOST PARTUM THYROIDITIS

Definition:Definition:

Silent thyroiditis of the Postpartum periodSilent thyroiditis of the Postpartum period

Flare up of a chronic autoimmune process Flare up of a chronic autoimmune process occurring in the first year after deliveryoccurring in the first year after delivery

Table 1 -Possible types of postpartum thyroid dysfunctIon

Prevalence .

Hyperthyroidism then hypothyroidism Commonest (70%) Hypothyroidism alone Common (20%) Hyperthyroidism alone Less common (5%)

Hypothyroidism then hyperthyroidism Rare

Table 2- Possible causes of postpartum hyperthyroidIsm

Common (> 95%) Prevalence* .

Painless thyroiditis: first attack vs. recurrence 70-80%

Graves' disease: first attack vs. recurrence 10-15% Rare {< 3-5%) Toxic nodular goitre (single vs. multiple nodules) Painful (typical) subacute thyroiditis lodine-induced (Jodbasedow) Thyrotoxicosis factitia

*Author's estimates based upon a summary of personal observations in Toronto, Canada, and those of others in Canada, Japan, & the United States and Sweden.

Survey Toronto, CanadaSurvey Toronto, Canada

AIMS: AIMS:

1)1) Prevalence of PPTDPrevalence of PPTD2)2) Characteristics of PPTD seenCharacteristics of PPTD seen

1376 randomly selected mothers enrolled 1376 randomly selected mothers enrolled immediately postpartum followed prospectively immediately postpartum followed prospectively for two yrsfor two yrs

495 (36%) completed at least 3 mos f/u495 (36%) completed at least 3 mos f/u

300(22%) completed 1yr f/u300(22%) completed 1yr f/u

(Walfish et. al. 1992)J Endocrinol Invest

Type PPTDType PPTD ## Minimal Minimal Prevalence Prevalence raterate

PPT (typical)PPT (typical) 4444 3.2%3.2%

Transient hyperthyroidismTransient hyperthyroidism 1717 1.25%1.25%

Hypothyroidism onlyHypothyroidism only 1717 1.25%1.25%

Graves’ HyperthyroidismGraves’ Hyperthyroidism 33 0.2%0.2%

TMNGTMNG 11 0.07%0.07%

TOTALTOTAL 8282 6.0%6.0%

PREVALENCEPREVALENCE

Ranges 5-10%Ranges 5-10%

Probably much more commonProbably much more common

PATHOPHYSIOLOGYPATHOPHYSIOLOGYAcute phase of Autoimmune thyroid dysfunctionAcute phase of Autoimmune thyroid dysfunction

1)1) Relationship between presence of TPO antibodies and occurrence of Relationship between presence of TPO antibodies and occurrence of PPTPPT

2)2) Histology of PPT (focal organized and diffuse destructive lymphocytic Histology of PPT (focal organized and diffuse destructive lymphocytic thyroiditis)thyroiditis)

3)3) Presence in the circulation of activated T-cells in postpartum patientsPresence in the circulation of activated T-cells in postpartum patients

4)4) Associations between the genetic inheritance of MHC molecules and Associations between the genetic inheritance of MHC molecules and the occurrence of PPTthe occurrence of PPT

5)5) PPT frequently leads to permanent autoimmune thyroid failurePPT frequently leads to permanent autoimmune thyroid failure

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

ROLE OF TPO ANTIBODIESROLE OF TPO ANTIBODIES

Is there a real association???Is there a real association???

1)1) TPO is only expressed at the apical border of TPO is only expressed at the apical border of thyroid follicular cells hardly accessible to thyroid follicular cells hardly accessible to circulating antibodies circulating antibodies

2)2) Circulating TPO antibodies found in a number of Circulating TPO antibodies found in a number of euthyroid elderly womeneuthyroid elderly women

ROLE OF TPO ANTIBODIESROLE OF TPO ANTIBODIES

1)1) TPO Ab does not seem to be the primary TPO Ab does not seem to be the primary disruptive event in the pathogenesis of disruptive event in the pathogenesis of PPTPPT

2)2) Serves as a marker of disease activity for Serves as a marker of disease activity for PPTPPT

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

CD4 HELPER T-CELLSCD4 HELPER T-CELLS

1)1) TH2:TH2: • Stimulate B-lymphocytes to produce Stimulate B-lymphocytes to produce

antibodies (TPO, TG) through cytokines antibodies (TPO, TG) through cytokines

2)2) TH1:TH1:• Stimulate cell destruction Stimulate cell destruction

• Activate macrophages and natural killer Activate macrophages and natural killer cells via cytokines such as gamma cells via cytokines such as gamma interferon to kill target cellsinterferon to kill target cells

CD8 T-CELLS CD8 T-CELLS

• Destroy target cellsDestroy target cells

• Recognize autoags directly on target cells Recognize autoags directly on target cells when in the context of MHC class I when in the context of MHC class I moleculesmolecules

• Kill via perforin and other cytokine Kill via perforin and other cytokine moleculesmolecules

APOPTOSISAPOPTOSIS

• Proapoptotic and antapoptotic factors also Proapoptotic and antapoptotic factors also act in target cells under attack. act in target cells under attack.

• Balance of CD95 receptor signalling death Balance of CD95 receptor signalling death with bcl-2 and CFLIP antiapoptotic familywith bcl-2 and CFLIP antiapoptotic family

• Interferon also promotes apoptosis through Interferon also promotes apoptosis through caspase and CD95 upregulation.caspase and CD95 upregulation.

PREDISPOSING FACTORSPREDISPOSING FACTORS

1)1) Personal or Family hx of Thyroid disease Personal or Family hx of Thyroid disease (Primarily Hashimoto’s)(Primarily Hashimoto’s)

2)2) Previous PPTPrevious PPT

3)3) TPO Ab titres in 1TPO Ab titres in 1stst trimester ( assoc with 30-35% trimester ( assoc with 30-35% incidence PPT)incidence PPT)

4)4) Other endocrine autoimmune disorders (esp Other endocrine autoimmune disorders (esp Type 1 DM)Type 1 DM)

PREDISPOSING FACTORSPREDISPOSING FACTORS

5)5) White and Asian women as opposed to blacks White and Asian women as opposed to blacks

6)6) Cigarette smoking Cigarette smoking

altered production proinflammatory cytokines in altered production proinflammatory cytokines in lung ???lung ???

• No effect maternal age, parity, presence of No effect maternal age, parity, presence of goiter, breast feeding, infant birthweight, on the goiter, breast feeding, infant birthweight, on the incidence of PPTincidence of PPT

DIAGNOSIS AND TREATMENTDIAGNOSIS AND TREATMENT

Thyrotoxicosis:Thyrotoxicosis:

• RULE OUTRULE OUT

1)1) GH : High RAIU, TBII +, Opthalmopathy, more GH : High RAIU, TBII +, Opthalmopathy, more symptomatic and persistssymptomatic and persists

2)2) Subacute thyroiditis: neck pain, increase ESR, Subacute thyroiditis: neck pain, increase ESR, low RAIUlow RAIU

3)3) TMNG: high RAIU, scan lights up in spotsTMNG: high RAIU, scan lights up in spots

DIAGNOSIS AND TREATMENTDIAGNOSIS AND TREATMENT

Other parameters studied:Other parameters studied:

Serum TG elevated in both GH and PPTSerum TG elevated in both GH and PPT

US echogenicity correlates well with thyroid US echogenicity correlates well with thyroid dysfunction but can also be seen in GHdysfunction but can also be seen in GH

High TPO Ab titres assoc with PPTHigh TPO Ab titres assoc with PPT

TREATMENTTREATMENT

• Usually unnecessaryUsually unnecessary

• Symptomatic treatment with b-blockers Symptomatic treatment with b-blockers which must soon be tapered and which must soon be tapered and discontinued as the thyrotoxic phase quickly discontinued as the thyrotoxic phase quickly resolvesresolves

• Monitor TSH, FT4 q monthlyMonitor TSH, FT4 q monthlyrisk of risk of hypothyroidismhypothyroidism

HYPOTHYROID PHASEHYPOTHYROID PHASE

Dx:Dx:

TSH, FT4TSH, FT4Tx: Tx:

T4 (50-75ug) if clinically symptomatic for 6-12 T4 (50-75ug) if clinically symptomatic for 6-12 months or at least 1 yr postpartum as 80% will be months or at least 1 yr postpartum as 80% will be euthyroid by yr 1euthyroid by yr 1

Subsequently follow TFTs q 6 months since risk Subsequently follow TFTs q 6 months since risk hypothyroidismhypothyroidism

WHAT TO WARN PATIENTS WHAT TO WARN PATIENTS ABOUT?ABOUT?

1.1. Risk of hypothyroidismRisk of hypothyroidism

• Jansson et al: 30% prevalence end yr 5Jansson et al: 30% prevalence end yr 5

• Othman et al: followed 43 pts with PPT Othman et al: followed 43 pts with PPT during 2-4 yr periodduring 2-4 yr period 23% women 23% women developed permanent hypothyroidism developed permanent hypothyroidism compared to none of the 173 controlscompared to none of the 173 controls

STUDY: PPT AND LONG TERM STUDY: PPT AND LONG TERM THYROID STATUSTHYROID STATUS

• Followed 98 TPO Ab + and 70 TPO Ab – Followed 98 TPO Ab + and 70 TPO Ab – women over 66-140 monthswomen over 66-140 months

• 24.5% TPO Ab + developed subclinical 24.5% TPO Ab + developed subclinical hypothyroidism c/w 1.4% of the TPO ab –hypothyroidism c/w 1.4% of the TPO ab –controls.controls.

Premawardhana et al. 2000 JCEM 85: 71-75

STUDY (cont’d)STUDY (cont’d)A.A. Hypothyroid form of PPTDHypothyroid form of PPTD

B.B. High TPO Ab levelsHigh TPO Ab levels

C.C. Hypoechogenic ultrasound patternHypoechogenic ultrasound pattern

• Led to a high relative risk of 32 of long Led to a high relative risk of 32 of long term thyroid dysfunction in TPO Ab+ PPT term thyroid dysfunction in TPO Ab+ PPT + c/w TPO Ab- PPT – controls+ c/w TPO Ab- PPT – controls

• Long term surveillence of TPO Ab + and Long term surveillence of TPO Ab + and PPTD positive women is requiredPPTD positive women is required

2.2. Recurrent PPTRecurrent PPT

• 70 % recurrence rate70 % recurrence rate

WHAT TO WARN PATIENTS WHAT TO WARN PATIENTS ABOUT?ABOUT?

3.3. Conception and PregnancyConception and Pregnancy• Positive TPO +/- Tg antibodies in 1Positive TPO +/- Tg antibodies in 1stst trimester trimester

pregnancy is a RF for spontaneous fetal loss pregnancy is a RF for spontaneous fetal loss • Studied 552 consecutive women in 1Studied 552 consecutive women in 1stst trimester trimester

of pregnancy and found that the spontaneous of pregnancy and found that the spontaneous abortion rate in thyroid Ab positive women was abortion rate in thyroid Ab positive women was significantly higher than in Ab negative women significantly higher than in Ab negative women (17 vs 8.4%)(17 vs 8.4%)

• Mechanism: defective immune system failing to Mechanism: defective immune system failing to become tolerant to the fetus or mild thryoid become tolerant to the fetus or mild thryoid insufficiency remains uncertaininsufficiency remains uncertain

WHAT TO WARN PATIENTS WHAT TO WARN PATIENTS ABOUT?ABOUT?

Stagnara-Green et al 1990 JAMA 264Stagnara-Green et al 1990 JAMA 264

4.4. OffspringOffspring

• Pop et al.1999 Clinical Endocrinology Pop et al.1999 Clinical Endocrinology 50:149-15550:149-155

• FT4 levels less than the 10FT4 levels less than the 10thth percentile percentile (irrespective of TSH or TPO status) at 12 (irrespective of TSH or TPO status) at 12 wks gestation significant risk factor for wks gestation significant risk factor for impaired psychomotor developmentimpaired psychomotor development

WHAT TO WARN PATIENTS WHAT TO WARN PATIENTS ABOUT?ABOUT?

OFFSPRING (cont’d)OFFSPRING (cont’d)

• Haddow et al. 1999 (NEJM 341;549-555)Haddow et al. 1999 (NEJM 341;549-555)

• Children born to mothers with hypothyroidism Children born to mothers with hypothyroidism during the 2during the 2ndnd trimester pregnancy as determined trimester pregnancy as determined by an elevated TSH have lower IQ scores and by an elevated TSH have lower IQ scores and more educational difficulties at age 7-9 yrs than more educational difficulties at age 7-9 yrs than children born to mothers with normal TSH during children born to mothers with normal TSH during pregnancypregnancy

• Chronic autoimmune thyroiditis is the most Chronic autoimmune thyroiditis is the most frequent cause of low normal FT4 and raised TSH frequent cause of low normal FT4 and raised TSH in women.in women.

SHOULD WE SCREEN FOR PPT?SHOULD WE SCREEN FOR PPT?

Must satisfy 4 questions:Must satisfy 4 questions:

1.1. Is PPT prevalent?Is PPT prevalent?

Yes 5-10%Yes 5-10%

2. & 3.2. & 3. COMORBIDITIES AND TREATMENT? COMORBIDITIES AND TREATMENT?

i.i. 25% develop primary hypothyroidism within 5 yrs 25% develop primary hypothyroidism within 5 yrs of deliveryof delivery

• No known interventions can decrease high No known interventions can decrease high rate of permanent hypothyroidismrate of permanent hypothyroidism

ii.ii. 70% chance of recurrent PPT70% chance of recurrent PPT

• Does T4 prevent recurrence?Does T4 prevent recurrence?

• T4 0.1mg daily from wk 4-38 and 0.05 mg T4 0.1mg daily from wk 4-38 and 0.05 mg from 39-42 wks postpartum in 18 TPO+ from 39-42 wks postpartum in 18 TPO+ womenwomen

ResultsResults

1.1. No change in the incidence or time course of No change in the incidence or time course of PPTPPT

2.2. degree of hypothyroidism was significantly degree of hypothyroidism was significantly reduced compared with 20 untreated Ab + reduced compared with 20 untreated Ab + womenwomen

LT4 & RECURRENCELT4 & RECURRENCE•Kampe et al 1990 JCEM 70: 1014-1018Kampe et al 1990 JCEM 70: 1014-1018

LT4 & RECURRENCELT4 & RECURRENCE

TSH in vitro increases the expression of TSH in vitro increases the expression of thyroid microsomal antigen and in the thyroid microsomal antigen and in the presence of gamma interferon increases presence of gamma interferon increases HLA class 2 expression on thyrocytes HLA class 2 expression on thyrocytes

Believed that thyroid doses given were not Believed that thyroid doses given were not as high as anticipated since 9 of the 18 as high as anticipated since 9 of the 18 women still had TSH values above 5 mU/L women still had TSH values above 5 mU/L despite treatment. despite treatment.

iii.iii. Increased rate of spontaneous abortionIncreased rate of spontaneous abortion

• Vaquero et al (2000)Am J Reprod Vaquero et al (2000)Am J Reprod Immunology 43:204-208Immunology 43:204-208

• Data suggested recurrent miscarraige in Data suggested recurrent miscarraige in women with thyroid antibodies can be women with thyroid antibodies can be prevented by T4 prevented by T4

iv.iv. Offspring psychomotor developmentOffspring psychomotor development

• Unknown if T4 replacement will Unknown if T4 replacement will effectively prevent neuropsychological effectively prevent neuropsychological abnormalities in the offspringabnormalities in the offspring

CURRENT SCREENING CURRENT SCREENING RECOMMENDATIONSRECOMMENDATIONS

Two specific populations would clearly benefit from Two specific populations would clearly benefit from screening:screening:

1.1. Women with previous hx of PPT (prevalence of Women with previous hx of PPT (prevalence of recurrent PPT =70%)recurrent PPT =70%)

2.2. Women with Type 1 diabetes (prevalence of PPT Women with Type 1 diabetes (prevalence of PPT =25%)=25%)

Measure TSH at 3 and 6 months post partumMeasure TSH at 3 and 6 months post partum

Women with increased of decreased TSH require Women with increased of decreased TSH require further investigations.further investigations.

PP DEPRESSION AND PPTD PP DEPRESSION AND PPTD LINKED?LINKED?

Postulated mechanism:Postulated mechanism:

• Hypothyroidism can reduce central Hypothyroidism can reduce central hydroxytryptamine neurotransmissionhydroxytryptamine neurotransmission

• Some believe cytokines released during Some believe cytokines released during autoimmune eg IL-6 and IL-1 interact with autoimmune eg IL-6 and IL-1 interact with neurotransmission cause problemsneurotransmission cause problems

PP DEPRESSION AND PPTD PP DEPRESSION AND PPTD LINKED?LINKED?

• Recent studies Oretti et al (2002) show Recent studies Oretti et al (2002) show excess of depression in general related to excess of depression in general related to positive thyroid antibody status rather than positive thyroid antibody status rather than to PPTD to PPTD

• They believe it is due to subtle changes in They believe it is due to subtle changes in thyroid hormone levelsthyroid hormone levels

International Journal of Social Psychiatry, in press

DOES L-T4 PREVENT DEPRESSION DOES L-T4 PREVENT DEPRESSION IN TPO AB POSITIVE WOMEN??IN TPO AB POSITIVE WOMEN??

AIM :AIM : to test that stabilising thyroid function pp by to test that stabilising thyroid function pp by administrating daily T4 reduces the rate of administrating daily T4 reduces the rate of occurrence and severity of associated depression.occurrence and severity of associated depression.

METHOD:METHOD: randomised double blind placebo controlled trail randomised double blind placebo controlled trail 100ug of T4 or placebo were given daily to 446 100ug of T4 or placebo were given daily to 446

TPO AB + (342 were compliant) for 6 wks to 6 TPO AB + (342 were compliant) for 6 wks to 6 months ppmonths pp

Psychiatric and thyroid status checked q 4 wkly Psychiatric and thyroid status checked q 4 wkly RDC for depressive disorder and Asberg RDC for depressive disorder and Asberg

depression Rating scaledepression Rating scaleHarris et. al. 2002 British Journal of Psychiatry 180:327-330

RESULTSRESULTS

1)1) Rates of depression and major Rates of depression and major depression at each visit were similar in depression at each visit were similar in both groupsboth groups

2)2) Overall rate of major depression was Overall rate of major depression was 18.5%18.5%

OVERALL RESULTSOVERALL RESULTS

1.1. Rates of depression here were similar to study Rates of depression here were similar to study by Harris et. al. 1992by Harris et. al. 1992

2.2. Positive TPO Ab associated with PPDPositive TPO Ab associated with PPD

3.3. T4 administration does not reduce post natal T4 administration does not reduce post natal depressiondepression

• Abnormal biochemical thyroid function has no Abnormal biochemical thyroid function has no effect rather TPO Ab status and number of effect rather TPO Ab status and number of negative events has impactnegative events has impact

FINAL CONCLUSIONSFINAL CONCLUSIONS

• High PrevalenceHigh Prevalence

• Pathogenesis unknownPathogenesis unknown

• Significant morbiditiesSignificant morbidities

• Some prevented by L-T4Some prevented by L-T4

• Screening effective with TSH in certain Screening effective with TSH in certain groupsgroups

What happened to my patient???What happened to my patient???

• 2 yrs later2 yrs later

• C/o chronic fatigue, wt loss, irritability and C/o chronic fatigue, wt loss, irritability and palpitationspalpitations

• High Ft4, Suppressed TSH, serum A-TG High Ft4, Suppressed TSH, serum A-TG and A-Mc weakly positiveand A-Mc weakly positive

• 24 hr uptake 40% , TBII positive 51%, 24 hr uptake 40% , TBII positive 51%, diffuse uptake on scandiffuse uptake on scan

• RX: PTU than ablationRX: PTU than ablation

• HLA haplotyping revealed susceptibility HLA haplotyping revealed susceptibility alleles associated with GH and PPTalleles associated with GH and PPT

PROPOSED MECHANISMPROPOSED MECHANISM

• Immunological activation of a destructive Immunological activation of a destructive thyroiditis releases thyroid antigenthyroiditis releases thyroid antigen

• Inflammatory response accompanied by a Inflammatory response accompanied by a lymphocytic infiltrate : APC, CD8 cytotoxic lymphocytic infiltrate : APC, CD8 cytotoxic T cellsT cells

• Activate TH1 cells of destruction and Activate TH1 cells of destruction and reciprocally suppress the TH2 pathwayreciprocally suppress the TH2 pathway

MECHANISM (cont’d)MECHANISM (cont’d)

In genetically predisposed mothers In genetically predisposed mothers

Released thyroid Ag triggers Released thyroid Ag triggers immune cascade immune cascade activates TH2 pathway activates TH2 pathway B-cellsB-cells TSH Receptor AbTSH Receptor Ab

When Ab sufficient levels When Ab sufficient levels GH clinically and GH clinically and biochemically evidentbiochemically evident

PRIMARY LESION THEORY OF PRIMARY LESION THEORY OF AUTOIMMUNITYAUTOIMMUNITY

• Preexisting injury plays an important role:Preexisting injury plays an important role: In development In development of persistent autoimmune endocrine dysfunction in those of persistent autoimmune endocrine dysfunction in those individuals with an underlying genetic susceptibility individuals with an underlying genetic susceptibility

Other Examples: Other Examples:

• Post parathyroidectomy painless thyroiditis with underlying Post parathyroidectomy painless thyroiditis with underlying autoimmune thyroiditisautoimmune thyroiditis

• Post Subacute thyroiditisPost Subacute thyroiditis

• Post I131 for TMNGPost I131 for TMNG

• External head and neck irradiationExternal head and neck irradiation