Diseases Of The Thyroid Gland.pdf

Diseases of the Thyroid Gland

DR L CHIN-HARTY MBBS REVIEW 2015

Thyroid Gland 

Located in the neck, anterior to the trachea



Produces T4 and T3



Regulated by negative feedback axis

Thyroid Gland 

T4 made exclusively in thyroid gland 

Ratio of T4 to T3 5:1



Potency of T4 to T3 1:10



T4 is the most important source of T3 by peripheral deiodination



More that 90% of the physiological effects are due to binding of T3 to thyroid receptors in peripheral tissues

Effects of Thyroid Hormone Affects every cell in the body. Modulates oxygen consumption, growth rate, maturation and cell differentiation, turnover of vitamins, hormones, proteins  Acts by binding to nuclear receptors, increasing protein synthesis  At mitochondrial level, increases number and activity to increase ATP production  At cell membrane increases ions and substrate transmembrane flux 

Effects of Thyroid Hormone 

Calorigenesis- controls the basal metabolic rate



CHO metabolism  Increases

glucose absorption of the git, glucose consumption by peripheral tissues, glucose uptake by the cells, glycolysis, gluconeogenesis



Growth & maturation rate

Effects of Thyroid Hormone 

CNS development & function 



Necessary in newborns, modulation of brain and mood modulation

Fat & protein metabolism 

Increase lipolysis & lipid mobilisation with cholesterol, triglycerides, free fatty acids



Muscle metabolism



Electrolyte balance

Effects of Thyroid Hormone 

Vitamin metabolism



Hematopoietic system



Cardiovascular system 



Heart rate, cardiac output, peripheral resistance, oxygen consumption, arterial pressure

Gastrointestinal- modulate bowel movements and absorption



Pregnancy- growth rate, lactation

Disorders 

Functional  Hyperthyroidism

 Hypothyroidism



Neoplasms  Benign  Malignant

Hyperthyroidism

 Thyrotoxicosis-

state of thyroid hormone excess

 Hyperthyroidism-

the result of excessive thyroid gland function

Hyperthyroidism Symptoms 

Hyperactivity/ irritability/ dysphoria



Heat intolerance and sweating



Palpitations



Fatigue and weakness



Weight loss with increase of appetite



Hyperdefecation



Polyuria



Oligomenorrhoea, loss of libido

Hyperthyroidism Signs Tachycardia (AF)  Tremor  Goiter  Warm moist skin  Proximal muscle weakness  Lid retraction or lag  Gynecomastia 

Causes of Hyperthyroidism Most common causes 

Graves disease



Toxic multinodular goiter



Autonomously functioning nodule

Rarer causes 

Thyroiditis or other causes of destruction



Thyrotoxicosis factitia



Iodine excess (JodBasedow phenomenon)



Struma ovarii



Secondary causes (TSH or ßHCG)

Other Causes of Thyrotoxicosis 

Drugs: Iodine excess



Secondary hyperthyroidism 

TSH secreting pituitary adenoma



Thyroid hormone resistance syndrome

Graves Disease 

Autoimmune disorder



Abs directed against TSH receptor with intrinsic activity. Thyroid and fibroblasts



Responsible for 60-80% of Thyrotoxicosis



More common in women

Graves Disease Eye Signs N - no signs or symptoms O – only signs (lid retraction or lag) no symptoms S – soft tissue involvement (periorbital oedema) P – proptosis (>22 mm)(Hertl’s test) E – extra ocular muscle involvement (diplopia) C – corneal involvement (keratitis) S – sight loss (compression of the optic nerve)

Graves Disease Other Manifestations 

Pretibial mixoedema



Thyroid acropachy



Onycholysis



Thyroid enlargement with a bruit frequently audible over the thyroid

Diagnosis of Graves Disease 

TSH , free T4



Thyroid auto antibodies



Nuclear thyroid scintigraphy (I123, Te99)

Graves’ Disease 

Diagnosis: 

Low TSH, High FT4 and/or FT3



If eye signs are present, the diagnosis of Graves’ disease can be made without further tests



If eye signs are absent and the patient is hyperthyroid with or without a goitre, a radioiodine uptake test should be done.



Radioiodine uptake and scan:





Scan shows diffuse uptake



Uptake is increased

TSH-R Ab (stim) is specific for Graves’ disease. May be a useful diagnostic test in the “apathetic” hyperthyroid patient or in the pt who presents with unilateral exopthalmos without obvious signs or laboratory manifestations of Graves’ disease

Treatment of Graves Disease 

Reduce thyroid hormone production or reduce the amount of thyroid tissue  Antithyroid

drugs: propyl-thiouracil, carbimazole  Radioiodine  Subtotal thyroidectomy – relapse after antithyroid therapy, pregnancy, severe thyroid eye disease 

Symptomatic treatment  Propranolol

Treatment of Grave’s Disease 

A. Medical therapy: 

Antithyroid drug therapy:   



Most useful in patients with small glands and mild disease Treatment is usually continued for 12-18 months Relapse occurs in 50% of cases There are 2 drugs: 

Neomercazole (methimazole or carbimazole): start 30-40mg/D for 1-2m then reduce to 5-20mg/D.



Propylthiouracil (PTU): start 100-150mg every 6hrs for 1-2m then reduce to 50-200 once or twice a day



Monitor therapy with fT4 and TSH



S.E.: 5% rash, 0.5% agranulocytosis (fever, sore throat), rare: cholestatic jaundice, hepatocellular toxicity, angioneurotic edema, acute arthralgia

Management of Grave’s disease 

A. Medical therapy: 

Propranolol 10-40mg q6hrs to control tachycardia, hypertension and atrial fibrillation during acute phase of thyrotoxicosis. It is withdrawn gradually as thyroxine levels return to normal



Other drugs: 

Ipodate sodium (1g OD): inhibits thyroid hormone synthesis and release and prevents conversion of T4 to T3



Cholestyramine 4g TID lowers serum T4 by binding it in the gut

Management of Grave’s disease 

B. Surgical therapy: 

Subtotal thyroidectomy is the treatment of choice for patients with very large glands



The patient is prepared with antithyroid drugs until euthyroid (about 6 weeks). In addition 2 weeks before the operation patient is given SSKI 5 drops BID to diminish vascularity of thyroid gland



Complications (1%): 

Hypoparathyroidism



Recurrent laryngeal nerve injury

Management of Grave’s Disease 

C. Radioactive iodine therapy: Preferred treatment in most patients  Can be administered immediately except in: 



Elderly patients



Patients with IHD or other medical problems



Severe thyrotoxicosis



Large glands >100g



In above cases it is desirable to achieve euthyroid state first

Hypothyroidism occurs in over 80% of cases.  Female should not get pregnant for 6-12m after RAI. 

Management of Grave’s Disease 

Management of opthalmopathy: 

Management involves cooperation between the endocrinologist and the opthalmologist



A course of prednisone immediately after RAI therapy 100mg daily in divided doses for 7-14 days then on alternate days in gradually diminishing dosage for 6-12 weeks.



Keep head elevated at night to diminish periorbital edema



If steroid therapy is not effective external x-ray therapy to the retrobulbar area may be helpful



If vision is threatened orbital decompression can be used

Management of Grave’s Disease 

Management during pregnancy: 

RAI is contraindicated



PTU is preferred over neomercazole



FT4 is maintained in the upper limit of normal



PTU can be taken throughout pregnancy or if surgery is contemplated then subtotal thyroidectomy can be performed safely in second trimester



Breastfeeding is allowed with PTU as it is not concentrated in the milk

Treatment of Graves DiseaseSpecial consideration 

Thyroid Storm 

      

Life threatening exacerbation of thyrotoxicosis accompanied by fever, delirium, seizures, coma, vomiting, diarrhea, jaundice. Mortality rate is up to 30% even with treatment Usually precipitated by an acute illness such as stroke, infection, trauma, dka, surgery IV PTU Radioiodine Propranolol Glucocorticoids benzodiazepines

Thyroid storm (Thyrotoxic crisis) 

Initiate prompt therapy after free T4, free T3, and TSH drawn without waiting for laboratory confirmation.



Therapy



1. General measures: 

Fluids, electrolytes and vasopressor agents should be used as indicated



A cooling blanket and acetaminophen can be used to treat the pyrexia



Propranolol for beta–adrenergic blockade and in addition causesdecreased peripheral conversion of T4 T3 but watch for CHF. 

The IV dose is 1 mg/min until adequate betablockade has been achieved. Concurrently, propranolol is given orally or via NG tube at a dose of 60 to 80 mg q4h

Thyroid storm (Thyrotoxic crisis) Therapy  2. Specific Measures: 











PTU is the anti-thyroid drug of choice and is used in high doses: 1000 mg of PTU should be given p.o. or be crushed and given via nasogastric tube, followed by PTU 250mg p.o. q 6h. If PTU unavailable can give methimazole 30mg p.o. every 6 hours. One hour after the loading dose of PTU is given –give iodide which acutely inhibits release of thyroid hormone, i.e. Lugol’s solution 2-3 drops q 8h OR potassium iodide (SSKI) 5 drops q 8h. Dexamethasone 2 mg IV q 6h for the first 24-48 hours lowers body temperature and inhibits peripheral conversion of T4-T3 With these measures the patient should improve dramatically in the first 24 hours.

3. Identify and treat precipitating factor.

Hypothyroidism

Hypothyroidism Symptoms 

Tiredness and weakness



Dry skin





Weight gain with poor appetite

Feeling cold



Hoarse voice



Hair loss





Difficulty in concentrating and poor memory

Menorrhagia, later oligo and amenorrhoea



Paresthesias

Constipation



Impaired hearing



Hypothyroidism Signs Dry skin, cool extremities  Puffy face, hands and feet  Delayed tendon reflex relaxation  Carpal tunnel syndrome  Bradycardia  Diffuse alopecia  Serous cavity effusions 

Causes of Hypothyroidism 



Autoimmune hypothyroidism (Hashimoto’s, atrophic thyroiditis) Iatrogenic (I123treatment, thyroidectomy, external irradiation of the neck)



Drugs: iodine excess, lithium, antithyroid drugs, etc



Iodine deficiency



Infiltrative disorders of the thyroid: amyloidosis, sarcoidosis,haemochro matosis, scleroderma

Lab Investigations of Hypothyroidism TSH , free T4  Ultrasound of thyroid – little value  Thyroid scintigraphy – little value  Anti thyroid antibodies – anti-TPO  S-CK , s-Chol , s-Triglyceride  Normochromic or macrocytic anemia  ECG: Bradycardia with small QRS complexes 

Hypothyroidism 

Diagnosis: 

 

 





A iFT4 and hTSH is diagnostic of primary hypothyroidism Serum T3 levels are variable (maybe in normal range) +ve test for thyroid autoantibodies (Tg Ab & TPO Ab) PLUS an enlarged thyroid gland suggest Hashimoto’s thyroiditis With pituitary myxedema FT4 will be i but serum TSH will be inappropriately normal or low TRH test may be done to differentiate pituitary from hypothalamic disease. Absence of TSH response to TRH indicates pituitary deficiency MRI of brain is indicated if pituitary or hypothalamic disease is suspected. Need to look for other pituitary deficiencies. If TSH is h & FT4 & FT3 are normal we call this condition subclinical hypothyroidism

Treatment of Hypothyroidism 

Levothyroxine  If

no residual thyroid function 1.5 μg/kg/day

 Patients

under age 60, without cardiac disease can be started on 50 – 100 μg/day. Dose adjusted according to TSH levels

 In

elderly especially those with CAD the starting dose should be much less (12.5 – 25 μg/day)

Hypothyroidism- Special considerations 

   

Myxedema coma  Reduced level of consciousness, seizures, hypotension/shock, hypothermia, hyponatremia  Usually in elderly hypothyroid patients  High mortality rate  IV levothyroxine  Adrenal insufficiency may be precipitated by administration of thyroid hormone therefore hydrocortisone 100 mg IV q 8h is usually given until the results of the initial plasma cortisol is known. Thyroxine replacement in hypoadrenalism Pregnancy Elderly patients Coronary artery disease

Thyroiditis

Thyroiditis 

Acute: rare and due to suppurative infection of the thyroid



Sub acute: also termed de Quervains thyroiditis/ granulomatous thyroiditis – mostly viral origin



Chronic thyroiditis: mostly autoimmune (Hashimoto’s)

Acute Thyroiditis 

Bacterial – Staph, Strep



Fungal – Aspergillus, Candida, Histoplasma, Pneumocystis



Radiation thyroiditis



Amiodarone (acute/ sub acute)

Painful thyroid, ESR usually elevated, thyroid function normal

Sub Acute Thyroiditis Viral (granulomatous) – Mumps, coxsackie, influenza, adeno and echoviruses Mostly affects middle aged women, Three phases, painful enlarged thyroid, usually complete resolution

Rx: NSAIDS and glucocorticoids if necessary

Sub Acute Thyroiditis (cont) Silent thyroiditis No tenderness of thyroid Occur mostly 3 – 6 months after pregnancy 3 phases: hyper hypo resolution, last 12 to 20 weeks ESR normal, TPO Abs present Usually no treatment necessary

Clinical Course of Sub Acute Thyroiditis

Chronic Thyroiditis Hashimoto’s 

Autoimmune



Initially goiter later very little thyroid tissue



Rarely associated with pain



Insidious onset and progression



Most common cause of hypothyroidism



TPO abs present (90 – 95%)

Chronic Thyroiditis Reidel’s 

Rare



Middle aged women



Insidious painless



Symptoms due to compression



Dense fibrosis develop



Usually no thyroid function impairment

Thyroiditis 

The most common form of thyroiditis is Hashimoto thyroiditis, this is also the most common cause of long term hypothyroidism



The outcome of all other types of thyroiditis is good with eventual return to normal thyroid function

Multinodular goitres Cause: presence of areas of hyperplasia & areas of hypoplasia in gland. Appearance: Large, irregular, nodular goiter Effect: euthyroid & pressure effect Small risk of malignant transformation Thyroxine suppression therapy to reduce size

Multinodular goitres Table 17-1. Factors that may be involved in the evolution of multinodular goiter. PRIMARY FACTORS •Functional heterogeneity of normal follicular cells, most probably due to genetic and acquisition of new inheritable qualities by replicating epithelial cells. Gender (women) is an important factor. •Subsequent functional and structural abnormalities in growing goiters. SECONDARY FACTORS •Elevated TSH (induced by iodine deficiency, natural goitrogens, inborn errors of thyroid hormone synthesis) •Smoking, stress, certain drugs •Other thyroid-stimulating factors (IGF-1 and others) •Endogenous factor (gender)

Multinodular goitres Table 17-2. Natural goitrogens associated with Multinodular Goiter Goitrogens Agent Millet, soy beans Flavonoids

Action Impairs thyroperoxidase

Cassava, sweet potato, sorghum

Cyanogenic glucosides Inhibits iodine thyroidal metabolized to thiocyanates uptake

Babassu coconut

Flavoniods

Inhibits thyroperoxidase

Cruciferous vegetables: Cabbage, cauliflower, Broccoli, turnips

Glucosinolates

Impairs iodine thyroidal uptake

Seaweed (kelp)

Iodine excess

Inhibits release of thyroidal Hormones

Malnutrition, Iron deficiency

Vitamin A deficiencyIron deficiency

Increases TSH stimulationReduces hemedependent thyroperoxidase thyroidal activity

Selenium

Selenium deficiency

Accumulates peroxidase and cause deiodinase deficiency ; impairs thyroid hormone synthesis

Modified and adapted from Medeiros-Neto & Knobel, ref. 33

Toxic Multinodular Goitre 

Usually occurs in older pts with long-standing MNG



PE reveals a MNG that may be small or quite large and may even extend substernally



RAI scan reveals multiple functioning nodules in the gland or patchy distribution of RAI



Hyperthyroidism in pts with MNG can often be ppt by iodide intake “jodbasedow phenomenon”.



Amiodarone can also ppt hyperthyroidism in pts with MNG



Treatment: Same as for Grave’s disease. Surgery is preferred.

Thyroid Neoplasms

Adenomas 

Discrete solitary masses



Derived from follicular epithelium (ie follicular adenomas)



Not predecessors of malignancy



Mostly nonfunctional



Small percentage produce hormones

Adenomas 

Usually present as unilateral painless mass



Take up less radioactive iodine compared to normal cells- “cold” nodules ( 10% malignant)



Biopsy is the gold standard for diagnosis

Other benign tumors 

Cysts



Lipomas



Hemangiomas



Dermoid cysts



Teratomas (mainly in infants)

Thyroid Carcinomas 

Most appear in adults (papillary Ca may present in childhood)



Female predominance in the early and middle adult age groups



Most are well differentiated 

Papillary Ca 80%



Follicular Ca 15%



Medullary Ca 5%



Anaplastic Ca <5%

Prognosis of Thyroid Carcinomas Papillary

Best prognosis

Follicular Medullary Anaplastic

Worst prognosis

Papillary Carcinoma 

Most common of thyroid ca



Any age



Vast majority is associated with ionising radiation exposure



Solitary or multifocal nodules



Metastasise via lymph nodes

Follicular Carcinoma 

Second most common form



Increased incidence in areas of dietary iodine deficiency



Do no arise from preexisting adenomas



Present most often as “cold” solitary nodules



Metastasize via blood to lungs, bone and liver

Medullary Carcinoma   

 

 

A disease of the C cells (parafollicular cells) More aggressive than papillary or follicular carcinoma but not as aggressive as undifferentiated thyroid cancer It extends locally, and may invade lymphatics and blood vessels Calcitonin and CEA are clinically useful markers for DX and F/U 80% of medullary ca are sporadic and the rest are familial. There are 4 familial patterns: 

FMTC without endocrine disease



MEN 2A: medullary ca + pheochromocytoma + hyperparathyroidism



MEN 2B: medullary ca + pheochromocytoma + multiple mucosal neuromas



MEN 2 with cutaneous lichen amyloidosis

The familial syndromes are associated with mutations in the ret protooncogene (a receptor protein kinase gene on chrom. 10) Dx is by FNA bx. Pt needs to be screened for other endocrine abnormalities found in MEN 2. Family members need to be screened for medullary ca and MEN 2 as well.

Anaplastic Carcinoma 

Most aggressive



Predominantly in elderly patients in areas with endemic goiter



Death in <1 year



Distant metastases is common

Secondary Tumours 

Direct extensions from: larynx, pharynx, oesophagus etc.



Metastasis from: renal cell carcinoma, large intestinal carcinoma, malignant melanoma, lung carcinoma, breast carcinoma etc.

Cases 

29 year old Female felt a nodule in her neck incidentally while she was getting ready for work one morning.



She went to her GP, who ordered a thyroid ultrasound, which demonstrated a 2cm nodule in the right lobe of the thyroid.

Cases 

After thorough history and physical, what would you order first for this patient? 

A. Thyroid function tests (TSH, T4)



B. CT neck



C. MRI neck



D. Radioactive Iodine uptake scan



E. All of the above

Cases 

What would you order first for this patient?  A. Thyroid function tests (TSH, T4) It is important to first establish the patient’s thyroid function. This will help determine if the known thyroid nodule is hyperfunctioning, hypofunctioning, or nonfunctioning. At this point, you should also obtain Fine Needle Aspiration (FNA) with ultrasound guidance, if necessary, to obtain cells for cytopathology. This will help determine if nodule is benign or malignant

Cases 

Important points in history:



Family history of thyroid disease or thyroid cancer? 



Personal history of radiation to head/neck 



Familial syndromes (MEN) Increased risk of thyroid cancer

Hoarseness, SOB, difficulty swallowing 

Compressive symptoms of thyroid goiter

Cases 

Patient is sent for labs as well as FNA. Patient returns to clinic the following week with FNA report reading “follicular cells, cannot rule out follicular neoplasm”. Is surgery indicated for your patient at this time? 

Yes



No

Cases Surgery is indicated. Follicular cells on FNA can be a benign finding or may indicate follicular carcinoma. Follicular carcinoma cannot be diagnosed solely on FNA (normal thyroid contains follicular cells.) Perform at least hemithyroidectomy for tissue diagnosis

Tissue taken at time of surgery must be sent for pathology to evaluate for extracapsular extension, lymphovascular invasion, or metastasis. Therefore, in the case that follicular neoplasm is suspected based on H&P and FNA results, patient should be taken to surgery for pathologic diagnosis and treatment.

Complications of thyroidectomy -

Intraoperative -

Bleeding -

-

Damage to arteries/veins of neck

Postoperative presentation -

-

Injury to recurrent laryngeal nerve -

Unilateral: hoarseness

-

Bilateral: respiratory distress

Bleeding -

-

Expanding hematoma – causes compression, shortness of breath

Hypocalcemia -

-

If patient develops expanding neck hematoma postoperatively, treatment involves immediate opening of sutures to evacuate clot and return to OR to explore and stop bleed

Removal or injury to parathyroid glands or their blood supply

Scar

Case 2 A 50 year old housewife complains of progressive weight gain of 20 pounds in 1 year, fatigue, postural dizziness, loss of memory, slow speech, deepening of her voice, dry skin, constipation, and cold intolerance.  Physical examination: Vital signs include a temperature 96.8oF, pulse 58/minute and regular, BP 110/60. She is moderately obese and speaks slowly and has a puffy face, with pale, cool, dry, and thick skin. The thyroid gland is not palpable. The deep tendon reflex time is delayed.  Laboratory studies: CBC and differential WBC are normal. The serum T4 concentration is 3.8 ug/dl (N=4.5-12.5), the serum TSH is 1 uU/ml (N=0.2-3.5), and the serum cholesterol is 255 mg/dl (N<200). 

Case 2 

What is the likely diagnosis? 

Secondary hypothyroidism or tertiary hypothyroidism (less likely).



There are certain features that are very suggestive for hypothyroidism such as:



a deep voice



delayed Achilles' tendon reflex time



bradycardia

Case 3 

A 35 year old nurse complained of nervousness, weakness, and palpitations with exertion for the past 6 months. Recently, she noticed excessive sweating and wanted to sleep with fewer blankets than her husband. She had maintained a normal weight of 120 pounds but was eating twice as much as she did 1 year ago. Menstrual periods have been regular but there was less bleeding.



Physical examination: Pulse was 92/minute and BP was 130/60. She appeared anxious, with a smooth, warm, and moist skin, a fine tremor, a bounding cardiac apical impulse, a pulmonic flow murmur, and she couldn't rise from a deep knee bend without aid. Her thyroid contained 3 nodules, 2 on the right and one on the left with a total gland size of 60 grams (3 times normal size), all nodules being of firm consistency and there was no lymphadenopathy. Her eyes were not prominent (proptotic) and she had no focal skin thickening.



Laboratory studies: Serum T4=15.6 ug/dl and serum T3=250 ng/dl (N=80-160