thyroid disorders –...

Thyroid disorders – Hypothyroidism/Hyperthyroidism

Thyroid function

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Euthyreoidism: normal TSH (0.4-4.5 mU/L),

fT4 (12-22 pmol/L) és fT3 (2.5-6.5 pmol/L)

Primary thyroid dysfunction:

Subclinical hypothyroidism:

elevated TSH, normal fT4

Overt hypothyroidism:

elevated TSH, decreased fT4

Subclinical hyperthyroidism:

Very low TSH (<0.1), normal fT4 és fT3

Overt hyperthyroidism:

Very low TSH, increased fT4 és/vagy fT3

fT4: free thyroxine, fT3: free triiode-thyronine TSH: thyreotropin, TRH: thyreotropin-releasing hormone

Hypothyroidism

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Hypothyroidism frequency

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Overt hypothyroidism: 2 – 3 %,

Subclinical hypothyroidism: 6 – 8 %,

Most frequently: female patients around 40Y

Congenital hypothyroidism: 1 : 4000

Autoimmun hypothyroidism:

female: 4 : 1000 man: 1 : 1000

Hypothyroidism causes

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Primary: (98-99%) Definitive: Transient: - thyreoiditis (Hashimoto) - thyreoiditis (subacut, postpartum)

- iatrogen - iodine excess ((sub)totalis thyreoidectomy - medical therapy Irradiation) - drug induced (lithium és amiodarone , interferon, mitotane)

- iodine-deficiency - congenitale - infiltration

Secundary:

- Pituitary disorders (cancer, OP, irradiation)

Tertier: - Hypothalamic disorders

Symptoms

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

fatigue weakness

slowly Increased sleepness

Muscle weakness Cold intolarence

Weight gain Hairloss, skin dryness

Concentration/memory deficits

depression hoarseness

infertility Libido loss

galactorrhe Menstrual irregularity

bradycardy hypertension

obstipation hyporeflexia

Check-up

• Typical symptoms (in elderly just few symptoms)

• anamnestic: thyroid OP/irradition, drugs, co-morbidities

• Lab-tests: TSH, fT4, aTPO

• Thyroid ultrasound

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Thyroid ultrasound

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Normális thyroid Hashimoto-thyreoiditis

Hashimoto-thyreoiditis

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Chronic lymphocyte-infiltration in the thyroid tissue. Local inflammation, irreversible destruction of the tissue – definitive hypothyroidism

Autoantibodies

- anti-peroxidase AB

- Thyroglobulin AB

Co-morbidities:

Type 1 diabetes mellitus, Morbus Addison, vitiligo, atropic gastritis, myasthenia gravis, Sjörgen syndrome

Hashimoto-thyreoiditis histology

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Normal follicules Hashimoto-thyreoiditis

Treatment

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Levothyroxine-substitution: Levothyroxine half life time 7-8 day. Once a day Dosage: 1,6-1,7 mg/ ttkg TSH-control: 4 weeks after dosage change, long-term

yearly/halfyearly Drug intake: fasten, 30 min before breakfast with water (no

coffee)

Hyperthyroidism

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Hyperthyroidism causes Morbus Graves-Basedow

toxic adenom ( Morbus Plummer)

multinodular goiter

iodine-induction

hCG- pregnancy induced

Rare causes:

TSH-secreted pituitary adenom

hCG-secreted tumours

overdosage of thyroxine

struma ovarii

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Transient hyperthyroidism • Distruction of thyroid follicules: T4 and T3 secreted in the

bloodstrem

de Quervain subacut thyroiditis

silent thyreoiditis

postirradiation thyreoiditis

Transient hyperthyroidism with overt hypothyroidism

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Hyperthyroidism frequency

II. sz. Belgyógyászati Klinika

Morbus Graves-Basedow 5-10/100000

Toxic goiter or toxic adenom in advanced age

Amiodarone induced hyperthyroidism 2%

Role of iodine:

Iodine-rich region: relative lower incidency of hyperthyroidism, with high prevalence of Morbus Graves-Basedow

Iodine-arm region, relative higher frequency with higher prevalence of toxic goiter

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Hyperthyroidism signs

irritability Emotional lability

Tremor, hyperreflexia Increased body temperature

Tachycardy Atrial fibrillation

Congestive heart failure Myopathy

Osteoporosis Increased appetite with weight loss

Diarrhoe Elevated liver function lab test

Opthalmopathy Increased sweating

Infertility Menstrual disorders

increased libido with ED Accelerated metabolism

Hypertension Hairloss

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Diagnostic

• Anamnestic, physical examination

• Hormone-test: TSH, fT4, fT3

• Ultrasound

• Antibody (TRAb)

• Thyroid-scan: diffuse increased Tc-uptake

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Morbus Basedow Merseburg-triade: exophthalmus, goiter, tachycardy

• Thyroid dermopathy

• Endocrine ophthalmopathy

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Ultrasound and scan

Tc-uptake increased

ultrasound Scan

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Endokrin opthalmopathy

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Morbus Basedow treatment

30-40% has definitive treatment success

60-70% relapse.

Medical treatment (1-1,5 year long drug therapy

Definitive treatment: in case of relapse, drug-intolerance,

etc

I131-isotope or near-total thyreoidectomx

Adjuvant treatment

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Medical treatment Thyreostatics:

methimazol 30-60 mg/day (Metothyrin, 10 mg)

propylthiouracil 300-600 mg/day (Propycil, 50 mg)

Alternative medical treatmen:

lithium

iodine (Wolff-Chaikov-effect),

(potassium-perchlorate)

Adjuvant treatment

propranolol 120-320 mg/day, inhibit of T4-T3 conversion

steroid (in severe hyperthyroidism)

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Side effects of drugs

frequency: 3-12%, avarage: 4.3%

pruritus 2.2%

urticaria 0.5%

granulocytopenia 1.6%

agranulocytosis 0,1-0,5%

toxic hepatitis

cholestatic icterus

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Radio-iodine treatment

• In USA 70%, in Europe 10-20%.

• Long term hypothyroidism

• No pregnancy in the next 6-12 months

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Operation

• Near-total thyreoidectomy, no relapse (~ 100% hypothyroidism)

• Indication: large goiter with local press symptoms, nodular goiter, ophthalmopathy, planned pregnancy in 1 year

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Toxic nodular goiter

Ultrasoung Scana

Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Toxic nodular goiter

• Over hyperthyroidism – treatment indicated

• Subclinical hyperthyroidism „wait and see”.

• Drug treatment has transient success.

• Definitive treatment: I131-isotope or operation

II. sz. Belgyógyászati Klinika Semmelweis Egyetem II. sz. Belgyógyászati Klinika

Thyroid cancer

Peter Reismann

Thyroid nodule

- Thyroid nodule is a discrete lesion within the thyroid gland that is radiologically distinct from the surrounding thyroid parenchyma. - Only nodules >1 cm should be evaluated - No universal screening advice - Tastbar nodule: 5% female, 1% man - US found nodule: 19-67% up to many studies,

more frequent with age and in female gender - 3-5% of the nodules are malignant

Diff. Diagnostic possibilities • Thyroid

– Benign nodule • Folliculare adenoma • Lipoma • Dermoid cysts • Teratoma

– Malignant • Papillary, follicular, medullary, anaplastic cancer • Lymphome, metastatic tumors

– Others • Focal thyroiditis • Granulomatic • Cyst

• Non-thyroid – Parathyroid adenoma – Ductus thyreoglossus cysts – Lymph nodes

Medical check-up in case of thyroid nodule

1. Thyroid ultrasound

2. TSH measurement

3. (Tc-thyroid scan)

4. FNA of suspected lesions

5. (Calcitonin measurement)

6. (Genetic analysis)

Thyroid ultrasound

Lymph nodes

Fine needle aspiration

FNA cytology

Papillary cancer cytology

Thyroid cancer

• Papillary cancer

• Follicular cancer

• Hürthle-cells variant

• Medullar cancer

• Anaplastic cancer

• Metastases

• Lymphom

Thyroid cancer

Thyroid cancer

• 3-15% have initial metastatic disease

• 6-20% will have metastatic disease during follow-up

• Papillary cancer : lymphatic metastatic: lymph nodes

• Follicular cancer: hematogen metastatic: bones, lung

• Medullary cancer: hematogen metastatic: liver, bones, lung, lymph nodes

Preoperative Study

• Neck ultrasound

– Initial diameter, solitaer/ multiplex

– Lymph nodes

• FNA

• NO: Thyreoglobulin Serum-level, aTG, CT, MR, PET/CT

Mutation

• BRAF T1799A- Val600Glu 44% in papillary cancer

• RET/PTC rearrangement 10-30% in papillary cancer

• MAPK-kinase longlasting activation

• N/K RAS, PAX8/PPARgamma in follicular cc.

• TERT, TP53 other mutations

MAPK

• Activation of MAPK prohihibits thyroid hormone synthesis and the gene settlement of Na-I-transporter and TPO.

Tumor development

Therapy

• Surgical: near-total thyreoidectomy or lobectomy

• Lymph nodes removal

– Central – therapeutical indication

– Latera – positive FNA or prophylactic indication

Follow-up

• Neck ultrasound

• Thyreoglobulin and aTG serum level

– Perfect tumormarker, < 0.2 ng/ml

• Whole-body RAI (123/131)-scan

• CT

Additional treatment

• Radio-iodine therapy

– Adjuvant - tumor remnant

– Remnant ablation

- follow up

• TSH-suppression

• TKI-inhibitor

• Study drugs

• Etc…

RAI

• Iodine-Uptake TSH > 30 mU/L

– Levothyroxine-off for 4-6 weeks

– Recombinant TSH (Thyrogen)

• Indications:

– Metastatic disease

– Primary tumor > 4 cm

– Primary tumor is out of thyroid bed

– Lymph nodes metastates

– Histology: aggresive behaviour

RAI

TSH-Suppression

• TSH has proliferative effect on thyroid cells

• Supraphysiologic levothyroxine dose

– High risk patient TSH < 0.1 mU/L

– Intermediate risk patient TSH: 0.1-0.5 mU/L

– Low risk patient TSH: 0.2-2.5 mU/L

Beyond standard therapy

• RAI-refracter disease

• No external beam radiation

• No routine systematic adjuvant chemotherapy

• Local recurrence:

– Surgical removal

– Ethanol injection

– Radiofrequency ablation

• TKI: sorafenib (Nexavar)

• Iodine-uptake enhancement: selumetinib

Follow-up

• Excellent response: 10 years survival > 90%

• 6 months US, Tg+aTG

• After 1 year: re-stratifications

– T4-off Tg, aTG measurement and US

• 5 years TSH-suppression

Thank You!