2MEDICINE8 Thyroid Gland Disorders UERM2015B.pdf

2.8 DISORDERS OF THE THYROID GLAND Michael D. Rosario MD, FPSEM

Legend: Italicized: Recordings

August 16, 2013

CONGENITAL HYPOTHYROIDISM

Lecture outline: -Thyroid anatomy and physiology -Thyroid work up -Hypothyroidism -Hyperthyroidism -Thyroiditis -Special situations -Goiter -Thyroid cancer

ANATOMY AND PHYSIOLOGY OF THE THYROID GLAND

Figure 1. Anatomy of the thyroid

ANATOMY • 2 lobes + isthmus • Between cricoid cartilage and suprasternal notch • 12-20 grams, highly vascular and soft • 4 parathyroid glands posterior (behind the thyroid gland) o Removal: Hypocalcemia • Lateral nerves: Recurrent laryngeal nerves o Damage: Vocal cord paralysis ***Thyroidectomy may cause removal of parathyroid gland and damage to recurrent laryngeal nerves • Medullary C cells o Neural crest derivatives o Produce Calcitonin  Calcium lowering hormone  Minimal role in calcium homeostasis  Clinical significance: Tumor marker for medullary thyroid cancer DEVELOPMENT • Orchestrated by coordinated expression of several developmental factors: TTF1, TTF2 and paired homeobox 8 (PAX-8) o Expressed selectively but not exclusively in the thyroid gland o Dictate thyroid cell development o Induction of thyroid specific genes for the following proteins  Thyroglobulin (Tg)  Thyroid peroxidase (TPO)  Sodium iodide symporter (NIS)  Thyroid stimulating hormone receptor (TSH-R) o Clinical significance: Mutations in these transcription factors or their target genes leads to congenital hypothyroidism Sarah M. | Hezer | Mariz | April | Tsen | Victor

Figure 2. Congenital hypothyroidism

• •

Occurs in 1/4000 newborns Part of neonatal screening o Transplacental passage of MATERNAL thyroid hormone occurs before the fetal thyroid glands to function (11th week) and provides partial hormone support to a fetus with congenital hypothyroidism o Clinical significance: early detection through neonatal screening allows early replacement in newborns preventing potentially severe developmental abnormalities

*** Thyroid gland of fetus will be fully developed at 11 weeks AOG before this, supply depends on the transplacental passage of maternal hormone REGULATION OF THE THYROID AXIS

Figure 3. HPT Axis

Hypothalamus • TRH (Thyrotropin releasing hormone) • Major positive regulator of TSH synthesis and secretion Pituitary • TSH (Thyroid stimulating hormone) • Stimulates thyroid hormone synthesis secretion • 31kDa hormone with alpha and beta sub-units • Most useful physiologic marker of thyroid hormone production Thyroid stimulating hormone receptor (TSH – R) • G protein coupled receptor (GPCR) • α subunit of stimulatory G protein o Activates adenylyl cyclase leading to increased production of cyclic AMP • Recessive loss of function mutation=hypoplasia or hypothyroidism UERM 2015B

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• •

Dominant gain of function mutation = thyroid cell hyperplasia, goiter, autonomous function Somatic mutations=clonal expansion of affected thyroid cell=autonomously functioning thyroid nodules

Thyroid • Thyroid hormones • Low levels o Increase basal TSH production o Enhance TRH mediated stimulation of TSH • High levels o Rapidly and directly suppress TSH gene expression and secretion o Inhibit TRH stimulation of TSH IODINE TRANSPORT TO THYROID • • • •

Ingested iodine is bound to serum proteins (albumin) o Unbound iodine is excreted in urine Thyroid glands extracts iodine in the circulation in a highly efficient manner Iodine uptake the critical first step; mediated by NIS Clinical significance: o Iodine deficiency leads to goiter and possibly hypothyroidism and cretinism o Iodine oversupply through supplements or iodine enriched foods (kelp, shellfish) is associated with increased incidence of autoimmune thyroid disease

CRETINISM • •

•

Mental and growth retardation Affects children who: o Live in iodine deficient region o Not treated with iodine or thyroid hormone immediately during early life o Born to mothers with iodine deficiency which worsens the condition o Concomitant selenium deficiency Iodine supplementation has markedly reduced the prevalence of cretinism

IODINE DEFICIENCY Common sources of dietary iodine: Breads Cheese, Cow’s milk Eggs Frozen yogurt Ice cream Iodine-containing multivitamins Iodized table salt Saltwater fish Seaweed (dulce, nori) Soy sauce Shellfish Soy milk, Yogurt FIDEL – Fortification for Iodine Deficiency Elimination **Why salt? Does not spoil easily and consumed by a lot of people so effective vehicle. Table 1. Recommended Daily Intake

Children Non pregnant adults Pregnant and lactating women

Recommended intake 90-120 ug/day 150-250 ug/day 250 ug/day

IODINE UPTAKE - NIS  



Expressed at the basolateral membrane of the thyroid follicular cells Also present in salivary glands (parotid, submandibular), lactating breast and placenta but a lower levels (so if radioiodine is given, there will also be uptake in parotid which is NORMAL) Affected by dietary iodine intake o Low levels – increased NIS expression and iodine uptake; increased thyroid blood flow

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o



High levels – decreased NIS expression and iodine uptake Clinical significance o Radioactive iodine treatment for differentiated thyroid cancer o Mutation leads to a congenital hypothyroidism

*** Iodine uptake in thyroid cells is secondary to sodium iodide symporter. Iodide absorption (via NIS) transported out in the apex (via pedrin, a protein → Iodide oxidation (through hydrogen peroxide and TPO/thyroid peroxidase enzyme → After iodination, attached to tyrosine residue found in thyroglobulin converted to 3’ mono or 3’5’ di-iodo tyrosine → coupled to form T3 or T4 catalyze by thyroid peroxidase. Thyroglobulin is reabsorbed in follicular cells (where T3 and T4 are cleaved) → released of T3 and T4 in circulation. Excess MIT and DIT, iodine is removed by dehalogenase → iodine goes back to pool. ORGANIFICATION, COUPLING, STORAGE AND RELEASE • Iodide is transported to the apical membrane where to be oxidized in an organification reaction that involves TPO and hydrogen peroxide  The reactive iodine atom is added to selected tyrosyl residues within Tg  The iodotyrosines in Tg are then coupled via an ether linkage in a reaction that is also catalyzed by TPO forming either T4 or T3  After coupling, Tg is taken back into the thyroid cell, where it is processed in lysosomes to release T4 and T3.  Dehalogenase enzymes deiodinate uncoupled mono and diiodotyrosines (MIT, DIT) to recycle iodide THYROID PROTEINS

HORMONE

TRANSPORT

BINDING

Purpose of binding proteins:  Increase pool of circulating hormone  Delay hormone clearance  Modulate hormone delivery Thyroxine binding globulin (TBG)  Low concentration but high affinity for thyroid hormones = 80% Albumin  High concentration but low affinity = 10% T4 & 30% T3 Transthyretin (TTR aka TBPA)  10% T4 & little T3 Unbound hormones  Biologically available for tissues  T3 less tightly bound than T4 (99.7% T3 vs 99.98% T4)  But there is less unbound or Free T3 in the circulation because it is produced in lesser amounts and is cleared more rapidly

ABNORMALITIES OF THE THYROID HORMONE BINDING PROTEINS Disease condition X linked TBG deficiency – Absent TBG leads to rapid hormone clearance

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Total T3 &T4

Free T3 and T4

TSH

Clinical

Low

Normal

Normal

Euthyroid

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Pregnancy or OCP use – Increased estrogen levels -elevated TBG Euthyroid Hyperthyroxine mia Increased binding affinity for T4 or T3

NUCLEAR THYROID HORMONE RECEPTORS High

Normal

Normal or Low

High

Normal

Normal

Euthyroid

Euthyroid

DEIODINASES Figure 5. Thyroid hormone receptors

• •

Figure 4. Deiodinases



*** If hormone is in target cell, will be acted upon by deiodinases (removal of one iodine from T4). Active hormone: T3 

Table 2. Types of deiodinases

Location

T4 affinity Response to increased T4 Susceptibility to PTU

Type 1

Type 2

Thyroid, Liver, Kidneys

Pituitary, Brain, Brown Fat, Thyroid Placenta

Type 3 Placenta, CNS, Hemangiomas, Adult and Fetal Liver, Skeletal Muscle

Low

High

Increased

Decreased

Increased

High

Absent

Absent

Provide Inactivate T3 intracellular and T4 Physiologic T3 in specific Most important role tissues, source of source of Reverse T3 plasma T3 ***↑ in T4 results to ↑ type 1 (produces active hormone and source of Source of plasma T3 in thyrotoxic patients



ACTION OF THYROID HORMONES (TH) Child •  Adult •

•

Brain development Growth and development childhood

in

latter

stages

of

Primarily metabolism o Carbohydrate, lipid, protein and vitamin metabolism o Regulation of oxygen consumption Other actions on mood, cognition, heart, bone and muscle

NON- GENOMIC ACTION OF TH •

plasma T3 in thyrotoxic patient, but susceptible to PTU). Type 2 produces intracellular T3 in specific tissues. Type 3 produces reverse T3 and inactivating enzyme. Clinical significance: infant with very

Enter cells by passive diffusion and via the monocarboxylate 8 (MCT8) transporter High affinity to nuclear thyroid hormone receptors (TRs) α & β which are expressed in most tissues, but their relative expression levels vary among organs o TR α is particularly abundant in brain, kidney, gonads, muscle, and heart o TR β expression is relatively high in the pituitary and liver. o The TR β2 isoform is selectively expressed in the hypothalamus and pituitary, where it plays a role in feedback control of the thyroid axis. Receptors are occupied mainly by T3, reflecting T4 to T3 conversion by peripheral tissues, greater T3 bioavailability in the plasma, and receptors’ greater affinity for T3. The aporeceptors bind to corepressor proteins that inhibit gene transcription. Thyroid hormone binding dissociates these corepressors and allows the recruitment of coactivators that enhance transcription.

•

big hemangioma (high level of T3)→ inactivation of T3 and T4 resulting to congenital hypothyroidism

Major effects of T3 are mediated by nuclear Thyroid Hormone Receptor regulation of target gene transcription However, it has some non genomic action o Vasculature – reduced systemic vascular resistance which rapidly occurs o Acts on glucose transporters in certain tissues allowing increased uptake of glucose

THYROID HORMONES RESISTANCE •

•

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Autosomal dominant o Similar hormonal abnormalities found other family members Mutation leading to loss of thyroid hormone receptor function

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o

• • •

They also function as antagonists of the remaining normal thyroid hormone receptors Elevated unbound thyroid hormone levels Inappropriately normal or elevated TSH The resistance is partial hence signs and symptoms of hypothyroidism are not full blown o Goiter, attention deficit, mild IQ reduction, delayed skeletal maturation

***↑ Tg = sign of thyroid cancer recurrence and to rule out Thyrotoxicosis factitia (Thyrotoxicosis factitia: Tg is normal but px has symptoms of thyrotoxicosis, either faking it or taking thyroid medication). Among Ab, the best is TPO (best indicator of autoimmune thyroid illness). Table 4. Thyroid Antibodies in subset of population (%)

Patient Group

THYROID WORK UP THYROID FUNCTION TESTS • •

TSH Total T3 and Total T4 o Highly protein bound which can be affected by numerous factors (refer to abnormalities of thyroid hormone binding proteins) o Elevated when TBG is high (increased estrogen conditions) o Decreased when TBG is low (Androgens, Nephrotic syndrome)  Free T3 and Free T4 (unbound) o Represents the biologically available hormonal pool o Isolated Free T3 elevation occurs in 2-5% of patients (T3 toxicosis) o Normal FT3 may occur in 25% of patients with Hypothyroidism *** TSH and unbound hormones (total hormones are highly protein

General Population Grave’s Disease Autoimmune thyroiditis

TSH receptor Antibody

Thyroglobulin (TG) Antibody

Thyroid Peroxidase (TPO) antibody

0%

5-20%

8-27%

80-95%

50-70%

50-80%

10-20%

80-90%

90-100%

RADIONUCLIDE IMAGING The thyroid gland selectively transports radioisotopes of iodine (123I, 125I, 131I) and 99mTc pertechnetate, allowing thyroid imaging and quantitation of radioactive tracer fractional uptake.  Iodine uptake measures thyroid function  High in Graves’ Disease  Low in thyroiditis (hyperthyroid phase)

bound so affected by various factors) Table 3. Match the following

Thyroid Function Thyroid Condition 1. High TSH, Low FT4, Low FT3 2. Normal TSH, Low FT4, A. Central Hypothyroidism Low FT3 B. Subclinical Hyperthyroidism 3. Low TSH, Normal FT4, C. Autoimmune Normal Hypothyroidism FT3 D. Sick Euthyroid Syndrome 4. Low TSH, High FT4, E. Hyperthyroidism High FT3 5. Normal TSH and FT4, Low FT3 ***Answer: 1: C (Autoimmune hypothyroidism) – low production, compensatory action of pituitary 2: A (Central hypothyroidism) 3: B (Subclinical hyperthyroidism) - asymptomatic 4: E (Hyperthyroidism) 5: D (Sick euthyroid syndrome) (See Thyroid Patterns in Appendix) THYROID PROTEINS AND ANTIBODIES  Thyroglobulin (Tg) o Follow up of thyroid cancer o To rule out thyrotoxicosis factitia o Elevated in thyroiditis  Antibodies to thyroid proteins o Anti thyroglobulin (Anti Tg)  Follow up of thyroid cancer patients  Autoimmune thyroid illness (not routinely included) o Anti Thyroid Peroxidase (Anti TPO)  Autoimmune thyroid illness o Anti TSH receptor (TRAB)  TSH stimulating – Hyperthyroidism  TSH blocking – Hypothyroidism Sarah M. | Hezer| Mariz| April| Tsen |Victor

Figure 6. Thyroid Scan Imaging

Figure 7. Radionuclide Imaging: Whole Body Scan

***Whole body scan done after thyroid cancer treatment to check for metastasis. Notice pick-up in salivary gland (normal)

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ULTRASOUND OF THE THYROID





 Figure 8. Ultrasound of the Thyroid

***Nodule: hypoechoic compared to thyroid tissues, regular/defined border, no calcification. Only does Biopsy if there are suspicious features  Micro calcification  Increased vascularity especially in the center  Irregular/ill-defined border



Genetic Factors o HLA-DR and CTLA-4 polymorphisms account for approximately half of the genetic susceptibility to autoimmune hypothyroidism. o Both of these genetic associations are shared by other autoimmune diseases(type 1 diabetes mellitus, Addison’s disease, pernicious anemia, and vitiligo) Sex o Female preponderance: sex steroid effect on immune response vs X chromosome-related genetic factor Diet o A high iodine intake may increase the risk of autoimmune hypothyroidism by immunologic effects or direct thyroid toxicity Infection o Congenital Rubella syndrome associated with high frequency of autoimmune hypothyroidism o Viral thyroiditis does not induce subsequent autoimmune thyroid disease.

HYPOTHYROIDISM PATHOGENESIS

Figure 10. Pathogenesis of Hashimoto’s thyroiditis and Grave’s disease



Figure 9. Classifications of Hypothyroidism

*** Most common worldwide: iodine deficiency. In iodine sufficient areas: autoimmune or iatrogenic (See appendix for algorithm– evaluation of hypothyroidism) ***Request for the complete panel (TSH, FT3, FT4) if suspecting thyroid disease (to avoid delay and multiple blood extraction) AUTOIMMUNE HYPOTHYROIDISM Hashimoto’s or Atrophic Goitrous Thyroiditis Thyroiditis Marked lymphocytic Lymphocytic infiltration with Less pronounced infiltration germinal cell formation Atrophy of thyroid Almost completely Thyroid follicles follicles with absent absent colloid Fibrosis Mild to moderate Extensive ***Autoimmune hypothyroidism- 2nd most common, can present as atrophy or a goiter, subclinical, overt/clinical Histology

CD8 + cytotoxic T cells o Primary mediator o Perforin-induced cell necrosis o Granzyme B induced apoptosis  Local production of Cytokines o TNF, IFN, IL-1 o Impair thyroid cell function directly o Induce thyroid cells to express pro-inflammatory molecules o Renders thyroid cells more susceptible to apoptosis  B cells o Secondary role; merely amplifies ongoing autoimmune response o TPO ab: -Useful marker for autoimmunity - Complement fixation - Transplacental passage does not damage fetal thyroid o TSH receptor Ab: -Seen in 20% of patients with autoimmune hypothyroidism -Blocking antibodies which block TSH binding -Hypothyroidism and atrophy -Transplacental passage=neonatal hypothyroidism ***Autoimmune hypothyroidism: blocking antibodies leading to hypothyroidism and atrophy (remember there are 2 types of TSHreceptor antibodies; in autoimmune hypothyroidism it is the blocking type). Can be passed on the fetus resulting to neonatal hypothyroidism

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SIGNS AND SYMPTOMS 



Symptoms: o Tiredness, weakness o Dry skin o Feeling cold o Hair loss; thinning of outer third of eyebrows (Queen Anne’s sign) o Difficulty concentrating and poor memory o Constipation o Weight gain with poor appetite o Dyspnea o Hoarse voice o Menorrhagia o Paresthesia o Impaired hearing Signs o Dry coarse skin o Cool peripheral extremities o Puffy face, hands and feet(myxedema) o Diffuse alopecia o Bradycardia o Peripheral edema o Delayed tendon reflex relaxation o Carpal tunnel syndrome o Serous cavity effusions ***Decreased in metabolism (patient slows down literally)

  

Almost always occurs in the elderly Hypothermia also a risk factor Hypoventilation, leading to hypoxia and hypercapnia, plays a major role in pathogenesis. o Factors that impair respiration may precipitate myxedema coma: drug(sedative, anesthetics, antidepressants), pneumonia, congestive heart failure, myocardial infarction or cerebrovascular accidents. ***Most severe form of hypothyroidism/ an endocrine emergency TREATMENT 





TREATMENT 

Levothyroxine Replacement 1. Start levothyroxine replacement 1.6-1.8ucg/kg BW(100150ucg/day) 2. Check TSH every 6-8 weeks 3. Adjust dose by 12.5 to 25 ucg until TSH goal of Lower half of Normal range is achieved

Levothyroxine o Loading dose: 500 ucg o Maintenance dose: 50-100 ucg g/d o Route: Intravenous(preferred) or nasogastric tube (though aborption may be impaired in myxedema) Liothyronine(T3) o Dose: 10 to 25 ucg every 8-12 hour intravenously or via nasogastric tube. o Advocated because T4-T3 conversion is impaired in myxedema coma. o Excess liothyronine has the potential to provoke arrhythmias. o advocated due to T4 to T3 impaired conversion in cases of Myxedema coma; may be given in combination. Combined levothyroxine (200ucg) and liothyronine (25ucg) o Loading: levothyroxine(200ucg) and liothyronine(25ucg) o Maintenance: levothyroxine(50-100ucg/d) and liothyronine (10ucg every 8 hour) ***Use of liothyronine is advocated since in Myxedema coma, there is impairment in the conversion of T4 to T3.

HYPERTHYROIDISM Special situations: o Pregnancy: higher requirements; need to increase dose by 50 % and reduce after delivery o Elderly, coronary artery disease patients: starting dose 12.5-25 ug/day *** Taken 30 minutes before breakfast (if taken incorrectly can results





Thyrotoxicosis o State of thyroid hormone excess o Ex. Excessive intake of levothyroxine Hyperthyroidism o Thyrotoxicosis due to excessive thyroid function o Ex. Graves’ Disease

to poor absorption and patient may need higher dose). ONLY request for TSH every 6-8 weeks (FT3 and FT4=unnecessary). If TSH is

THYROTOXICOSIS

within target (lower half of normal range) no need to adjust (if high or low, adjust in this range: 12.5 to 25 ucg) 

Non-levothyroxine Replacement o Dessicated animal thyroid prepations (thyroid extract USP) are not recommended as the ratio of T3-T4 is nonphysiologic. o Benefit of using levothyroxine combined with liothyronine (triiodothyronine, T3) has not been confirmed in several prospective studies. o There is no place for liothyronine alone as long-term replacement, because the short half-life necessitates three or four daily doses and is associated with fluctuating T3 levels. ***For replacement, levothyroxine is preferred over liothyronine (since levothyroxine only required less dosage and can be taken once a day unlike liothyronine which required multiple dosages). Liothyronine is usually indicated for 1). preparing the patient for radioactive iodine uptake and 2). if allergic to levothyroxine (based on Dr. Rosario’s practice) MYXEDEMA COMA 

Clinical manifestations: Reduced level of consciousness, seizures, hypothermia  History of treated hypothyroidism with poor compliance, or the patient may be previously undiagnosed. Sarah M. | Hezer| Mariz| April| Tsen |Victor

Figure 11. Classification of thyrotoxicosis

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PATHOGENESIS 

Thyroid Stimulating Immunoglobulins (TSI) o Synthesized in the thyroid gland, bone marrow and lymph node o Aka TRAB



RISK FACTORS   

  

Polymorphism in HLA-DR, CTLA-4, CD25, PTPN22, TSHR Stress via the Neuroendocrine system Smoking o Minor risk: Graves’ disease o Major risk: TAO Postpartum Increased iodine uptake After use of HAART tx or alemtuzumab tx

SIGNS AND SYMPTOMS  Signs o Tachycardia; atrial fibrillation in the elderly o Tremors o Goiter o Warm, moist skin o Muscle weakness, proximal myopathy o Lid retraction or lab o Gynecomastia  Symptoms o Hyperactivity, irritability, dysphoria o Heat intolerance and sweating o Palpitations o Fatigue and weakness o Weight loss despite increased appetite o Diarrhea o Polyuria o Oligomenorrhea, loss of libido

o Achieve euthyroid status o Smoking cessation o Reassurance Mild-moderate o Artificial tears, eye ointment and use of dark glasses o Periorbital edema-upright sleeping position or diuretic o Eye patches when sleeping to avoid corneal exposure

***Elderly may have Apathetic Thyrotoxicosis: weight loss (some don’t – rather increases appetite), hyperdefecation, palpitation, heat intolerance, muscle weakness (proximal mostly affected) 

Severe ophthalmopathy o First line: high dose oral steroids or pulse steroids followed by oral steroids o Orbital decompression: removal of bone from any wall of the orbit o External beam radiotherapy

***Management is mostly supportive ; if severe: use High dose of Steroids (oral/IV) if not decompress by surgery – removing bone wall or radiotherapy. THYROID DERMOPATHY   

  

5% of the population o Women>Men o Greater prevalence of autoimmune thyroid disease o Increased iodine demands during pregnancy o TSH levels normal to slight increase only o But probably there is increased sensitivity to its effects o Patient will present OBSTRUCTIVE SYMPTOMS Goitrogens • Cassava root – thiocyanate • Cruciferous vegetables – brussels sprouts, cabbage, cauliflower • Milk from areas where goitrogens are present in grass • S/Sxs o Obstructive symptoms o Tracheal obstruction esp substernal goiter o dysphagia o External jugular vein - Pemberton’s sign Treatment: • Iodine replacement • Levothyroxine replacement • Young pxs: 100 mcg/day targeting low to normal TSH • Elderly: 50 mcg/day • Efficacy greater for younger pxs, soft goiters • Significant regression: within 3-6 months • Surgery: Near total thyroidectomy • Radioiodine: reduced goiter size by about 50% in the majority of pxs in 6-12 months NONTOXIC MULTINODULAR GOITER • •

Most nodules are polyclonal in origin TSH usually not elevated

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• • • •

Most are asymptomatic and euthyroid; Obstructive symptoms Ultrasound: Look for characteristics suggestive of malignancy Levothyroxine replacement rarely effective to reduce goiter size Radioiodine treatment may decrease goiter size by 4050%

TOXIC MULTINODULAR GOITER • • • • •

•

•

Presence of autonomously functioning nodules Subclinical or mild thyrotoxicosis Elderly patient: tremors, atrial fibrillation or weight loss Aggravated by recent exposure to iodine Anti thyroid drugs o May stimulate growth of goiter o Spontaneous remission does not occur – lifelong tx Radioiodine o Treat areas of autonomy and decrease goiter size o Treated areas may be replaced by other new autonomous nodules Surgery

WELL DIFFERENTIATED ***Classified according to histologic features Papillary • Most common 70-90% • Histology: Psammoma bodies, cleaved nuclei with an “orphan-Annie” appearance caused by large nucleoli, and the formation of papillary structures • Locally invasive Follicular • More common in iodine-deficient regions. • Difficult to diagnose by FNA because the distinction between benign and malignant follicular neoplasms rests largely on evidence of invasion into vessels, nerves, or adjacent structures • Hematogenous spread

Figure 17. Findings on thyroid scan: heterogenous uptake with areas of increased and decreased uptake

HYPERFUNCTIONING SOLITARY NODULE • • • • • •

Solitary autonomously functioning thyroid nodule Mild thyrotoxicosis Medical treatment is not an optimal long term treatment Radioiodine ablation Surgery: Enuceation or lobectomy Ethanol injections or percutaneous radiofrequency thermal ablation

Figure 18. Findings on thyroid scan: Focal uptake with diminished uptake in the remainder (normal tissue) as activity in those areas are suppressed

***Check TSH: if Decreased do thyroid scan – if INCREASED uptake – no need for BIOPSY, but if DECREASED uptake- do

Figure 20. Treatment of Well Differentiated

**Treatment: Surgery the RAI to destroy remaining tissues not removed by surgery, e.g. on Lymph nodes. Provided suppressive levothyroxine – Decreased TSH (note: TSH stimulates growth of thyroid cells) then monitor by blood test. POORLY DIFFERENTIATED Anaplastic • Poor prognosis • Poor response to radioiodine treatment • Chemotherapy ineffective Others: Medullary • Association with Multiple Endocrine Neoplasia 2 • Serum calcitonin is a marker of residual or recurrent disease Lymphoma • Rapidly expanding thyroid mass • Highly sensitive to external radiation (rapidly expanding!)

Biopsy, If purely cystic – no need for biopsy. SAMPLE CASES

THYROID CANCER Most common malignancy of the endocrine system

Case 1: Mr. Gollum. What is his problem (aside from losing the ring)?  Appears anxious, keeps muttering “my precious”

Figure 19. Findings on thyroid scan

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

HR elevated



BMI: 17



Neck mass with bruit



Irregularly irregular bruit



TSH low



FT4 and FT3 are high

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Case 2: Patient A at ICU bed 3 presents with palpitations on his 3rd HD (hospital day). TSH was requested which showed a suppressed TSH. Which of the following medications being given to him could explain this findings? a. Dobutamine b. Hydrocortisone c. Simvastatin d. Levothyroxine Anwer: both b&d – Dopamine, glucocorticoids and somastatin suppress TSH when these agents are administered in pharmacological doses. Case 3: Patient A came in for screening for thyroid disease. Which of the following times is the best time to perform the TSH? a. 8 am after overnight fast b. 12 noon c. 6 pm d. 12 mn Answer: any of the following is correct; since TSH has relatively long half-life and no need to undergo fasting. TSH is released in a pulsatile manner and exhibits a diurnal rhythm – highest level at night. However, TSH excursions are modest compared to other pituitary hormones because of TSH has a relatively long plasma half-life. Consequently, single measurements of TSH are adequate for assessing its circulating level.

a. Less than 90 ug/day b. 90-120 ug/day c. 150-250 ug day d. 250 ug/day Answer: D, refer to table of recommended daily intake Case: 5. Px F, a 34 yr old female came in with the following thyroid function results. Low T4 and T3 but normal Free T4 and TSH. What is your explanation for the thyroid function pattern? a. X linked TBG Deficiency b. Pregnancy c. OCP use d. Euthyroid Hyperthyroxinemia Answer: A Case 6 : SE is a 64/F admitted at the ICU for Heart Failure for the past 14 days referred for further evaluation of palpitations. She has no prior history of thyroid illness. No other signs or symptoms of thyroid dysfunction. Thyroid function tests showed low TSH, slightly high FT4, and low FT 3. Your impression is: A. Secondary hypothyroidism B. Hyperthyroidism C. Subacute Thyroiditis D. Sick Euthyroid Syndrome Answer: D

Case 4: Patient I came in for her prenatal check-up. She asks you, what is the recommended daily intake of iodine for a pregnant like her?

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APPENDIX

Figure 21. Evaluation of Hypothyroidism

Figure 22. Evaluation of Thyrotoxicosis

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Table 4. Thyroid Patterns

THYROID DISORDER Hyperthyroidism Subclinical Hyperthyroidism Primary Hypothyroidism Secondary Hypothyroidism

TSH

FRE T4

TOTAL T4

Low

High

High

SIGNS AND SYMPTOMS Present

Low

Normal

Normal

Absent

High

Low

Low

Present

Low or Inappropriately Normal

Low

Low

Absent/Present

Normal

Normal

Absent

Subclinical High Hypothyroidism Increased TBG Normal Decreased TBG Normal ***Primary hypothyroidism: ↑ TSH, pituitary is compensating, in

Normal Increased Absent Normal Decreased Absent secondary: problem is in pituitary or hypothalamus so ↓ TSH (inadequate

elevation in TSH or remain inappropriately normal since normal response is high and normal response means abnormal) ***↑ or ↓ TBG and total T4, but NORMAL, TSH and FT4, patient is asymptomatic

Figure 23. Methimazole vs Propylthiouracil Table 5. Comparison of drugs used to treat hyperthyroidism

PTU Methimazole Thiocyanate

INHIBIT ORGANIFIC ATION Yes Yes

IMPAIR CONVERSION OF T4 TO T3 BY D1 Yes (600mg)

IODIDE TRANSPORT INHIBITORS (NIS)

INHIBIT HORMONE RELEASE

ADDITIONAL INFO

Yes

3 drops BID with 7-10 day preop to decrease vascularity

Yes

Iodine (SSKI) IpodateIopanoate Lithium

Yes

Dexamethasone

Yes (additive to PTU)

Propanolol

Weakly

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Yes Yes

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Target Lithium: 1meq/L With addition of PTU and SSKI will produce rapid T3 decrease in 48 hours

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Figure 25. Burch Wartofsky Scoring

Figure 27. Approach to patient with thyroid nodule (ATA 2009 Guidelines for Thyroid Nodules & DTC)

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