1. Anterior Neck Mass
Sabalvaro Dyan, Salac Carmina, Salazar Janelle , Salazar Riccel, Salcedo Von, Saldana Emmanuel, Sales Stephanie, Salonga Cryscel

2. 65 year old female with anterior neck mass

3. History of Present Illness
5 years PTC
Noted presence of 2x2 cm anterior neck mass
No accompanying symptoms
4 years PTC
Progressive increase in size and felt a “lump in the throat” which prompted consult
Prescribed L thyroxine 100 ug/tab 1 tab TID which she took for one month until she noted easy fatigability, palpitations, and weight loss.
She consulted again and the physician requested for serum T3 ,T4, and TSH
after which she was advised to discontinue taking the medication.
Consult
Due to persistence of the mass, she sought consult at your clinic.

4. Physical Examination
Neck: 8 X 6 cm firm anterior neck mass with well‐defined borders and moves with deglutition
No palpable cervical adenopathies
BP=120/80 PR=85/min RR=28/min
Heart/Chest/Abdomen unremarkable
Pink palpebral conjunctive, anicteric sclerae

5. Salient Features Physical Examination 65 y/o Female
2 X 2 cm anterior neck mass
Progressive increase in size – “lump in throat
Prescribed L thyroxine 100 ug/tab 1 tab TID
took for one month until she noted easy fatigability, palpitations, and weight loss
Discontinued medication as advised by physician
Physical Examination
VS: BP=120/80 PR=85/min RR=28/min
Pink palpebral conjunctive, anicteric sclerae
Neck: 8 X 6 cm firm anterior neck mass with well‐defined borders and moves with deglutition; no palpable cervical adenopathies
Heart/Chest/Abdomen – unremarkable

6. 1. If you were the physician who initially saw the patient one year ago, what would you have done?

7. 2. What do you think were the serum T3 ,T4, and TSH levels in the previous consult? What do you call this condition?

8. Low circulating levels of T4 and T3 Primary Thyroid Failure
Raised TSH levels
Secondary Hypothyroidism
Low TSH levels that do not increase following TRH stimulation
LEVOTHYROXINE SODIUM
INDICATION
Hypothyroidism.
Adults: Initially mcg daily, and adjusted 4-6 week intervals by 50 mcg until attainment of clinical and biochemical euthyroidism. Normal metabolism is steadily maintained. This may require doses of mcg daily. With patients >50 years, it is not advisable to exceed 50 mcg a day initially. Where there is cardiac disease, 50 mcg on alternate days is more suitable. In this condition, the daily dosage may be increased by 50 mcg on alternate days is more suitable. In this condition, the daily dosage may be increased by 50 mcg on alternate days, at intervals of approximately 4 weeks.
OVERDOSAGE:
Symptoms: In addition to exaggeration of side effects, the following symptoms may be seen: Agitation, confusion, irritability, hyperactivity, headache, sweating, mydriasis, tachycardia, arrhythmias, tachypnea, pyrexia, increased bowel movements and convulsions. The appearance of clinical hyperthyroidism may be delayed for up to 5 days. Treatment: The goal of therapy is restoration of clinical and biochemical euthyroid state by omitting or reducing the Eltroxin dosage and other measures as needed depending on clinical status.
Treatment is symptomatic, and tachycardia has been controlled in adults by 40-mg doses of propranolol given every 6 hrs and other symptoms by diazepam and/or chlorpromazine as appropriate.
Further management should be as clinically indicated or as recommended by the national poison centre, where available.
C/I:
Hypersensitivity to any component of Eltroxin. Thyrotoxicosis.
SPECIAL PRECAUTIONS:
Eltroxin has a narrow therapeutic index. Appropriate Eltroxin dosage is based upon clinical assessment and laboratory monitoring of thyroid function tests. During the initial titration period, careful dosage titration and monitoring is necessary to avoid consequences of under- or over-treatment. The symptoms of excessive Eltroxin dosage are the same as many features of endogenous thyrotoxicosis.Patients with panhypopituitarism or other causes predisposing to adrenal insufficiency may cause reactions including dizziness, weakness, weight loss, hypotension and adrenal crisis. It is advisable to initiate corticosteroid therapy before giving thyroxine in these cases.
Special care is needed in the elderly and in patients with symptoms of myocardial insufficiency or ECG evidence of myocardial infarction or ischemia and also those with diabetes mellitus or insipidus.
Eltroxin raises blood sugar levels and this may upset the stability of patients receiving antidiabetic agents.
MOA:
Thyroxine (T4) is a naturally occuring hormone produced by the thyroid gland and converted to the more active hormone triiodothyronine (T3) in peripheral tissues. The precise signals controlling the conversion of T4 to T3 within the cell are not known. The thyroid hormones are required for normal growth and development , particularly of the nervous system. They increase the resting or basal metabolic rate of the whole organism and have stimulatory effects on the heart, skeletal muscle, liver and kidney. Thyroid hormones enhance lipolysis and the utilization of carbohydrate.

9. HYPOTHYROIDISM
Deficiency in the circulating levels of thyroid hormone leads to hypothyroidism, and, in neonates, to cretinism, which is characterized by neurologic impairment and mental retardation.
Hypothyroidism may also be associated with deafness (Pendred's syndrome)4 and Turner's syndrome.

11. In adults, symptoms in general are nonspecific:
Tiredness, weight gain, cold intolerance, constipation, and menorrhagia
Patients with severe hypothyroidism or myxedema
Facial and periorbital puffiness
Characteristic facial features as a consequence of the deposition of glycosaminoglycans in the subcutaneous tissues
The skin becomes rough and dry and often develops a yellowish hue from reduced conversion of carotene to vitamin A.
Hair becomes dry and brittle, and severe hair loss may occur
Loss of the outer two-thirds of the eyebrows.

12. Nonspecific abdominal pain accompanied by distention and constipation.
An enlarged tongue may impair speech, which is already slowed, in keeping with the impairment of mental processes.
Myxedema madness
Untreated dementia
Nonspecific abdominal pain accompanied by distention and constipation.
Libido and fertility are impaired in both sexes.
Cardiovascular changes in hypothyroidism include:
Bradycardia, cardiomegaly, pericardial effusion, reduced cardiac output, and pulmonary effusions
Cardiac failure is uncommon
When hypothyroidism occurs as a result of pituitary failure, features of hypopituitarism such as pale, waxy skin, loss of body hair, and atrophic genitalia may be present

13. LABORATORY FINDINGS
Hypothyroidism is characterized by low circulating levels of T4 and T3.
Raised TSH levels are found in primary thyroid failure, whereas secondary hypothyroidism is characterized by low TSH levels that do not increase following TRH stimulation.
Thyroid autoantibodies are present and are highest in patients with autoimmune disease (Hashimoto's thyroiditis, Graves' disease), although they are also elevated in patients with nodular goiter and thyroid neoplasms.
Other findings include anemia, hypercholesterolemia, and decreased voltage with flattening or inversion of T waves on electrocardiogram. Comatose patients with myxedema also have hyponatremia and CO2 retention.

14. TREATMENT THYROXINE Treatment of choice
50 to 200 mcg per day, depending upon patient's size and condition.
Starting doses of 100 mcg of thyroxine daily are well tolerated
Elderly patients and those with coexisting heart disease and profound hypothyroidism should be started on a considerably lower dose such as 25 to 50 mcg daily because of associated hypercholesterolemia and atherosclerosis.
The dose can be slowly increased over weeks to months to attain a euthyroid state.
EUTHYROID - The state of having normal thyroid gland function.

15. A baseline ECG should always be obtained in patients with severe hypothyroidism prior to treatment.
Patients are instructed to take tablets in the morning, usually without other medications, or at mealtime to assure good absorption.
Thyroxine dosage is titrated against clinical response and TSH levels, which should return to normal.
Patients who present with myxedema coma, in contrast to the patients with mild to moderate hypothyroidism, require an initial emergency treatment with large doses of intravenous thyroxine (300 to 400 g), and careful monitoring in an ICU setting.

16. 3. What is your diagnosis? Other considerations? Explain.

17. Diagnosis
Hyperthyroidism secondary to over dosage to L thyroxine

18. Other Considerations

19. Differential Diagnoses
Nodular Non-toxic Goiter
Graves’ Disease
Toxic Multinodular Goiter
Toxic Adenoma
Solitary Thyroid Nodule

20. Nodular Non-toxic Goiter
FAMILIAL GOITER
ENDEMIC GOITER
SPORADIC GOITER
Inherited enzyme defect
Impaired iodine metabolism
Usually associated with hypothyroidism
Due to iodine-deficient diet
Mountainous regions
intake of substances (goitrogens) that inhibit production of thyroid hormone—common goitrogens include foods such as cabbage, turnips, brussel sprouts, seaweed, and millet
Tx: iodized salt
No definite cause can be established

21. Enlargement of the thyroid gland No toxicity; no cancer
The following factors increase your chance of developing nontoxic goiter:
Sex: female (nontoxic goiter is more common in women than men)
Age: over 40 years
Reference:

22. SYMPTOMS Nontoxic goiters usually do not have noticeable symptoms.
Swelling on the neck
Breathing difficulties, coughing, or wheezing with large goiter
Difficulty swallowing with large goiter
Feeling of pressure on the neck
Hoarseness

23. MANAGEMENT
A goiter only needs to be treated if it is causing symptoms.
Treatments for an enlarged thyroid include:
Radioactive iodine to shrink the gland, particularly if the thyroid is producing too much thyroid hormone
Surgery (thyroidectomy) to remove all or part of the gland
Small doses of Lugol's iodine or potassium iodine solution if the goiter is due to iodine deficiency
Treatment with thyroid hormone supplements if the goiter is due to underactive thyroid
Reference:

24. INDICATIONS FOR SURGERY
Huge goiter which is cosmetically unacceptable
Compression symptoms
Suspicion of malignancy

25. GRAVES’ DISEASE
A type of hyperthyroidism, is caused by a generalized overactivity of the entire thyroid gland.
An autoimmune disease; thyroid-stimulating antibodies directed at TSH receptors on follicular cells.
It is named for Robert Graves, an Irish physician, who was the first to describe this form of hyperthyroidism about 150 years ago.

26. ETIOLOGY The trigger for auto-antibody production is not known.
Genetic predisposition – HLA DR3
Since Graves' disease is an autoimmune disease which appears suddenly, often quite late in life, it is thought that a viral or infection may trigger antibodies which cross- react with the human TSH receptor (a phenomenon known as antigenic mimicry, also seen in some cases of Type I diabetes).
Yersinia enterocolitica
Reference:

27. CLINICAL FEATURES Triad: Symptoms: Goiter including the pyramidal lobe
Thyrotoxicosis
Exophthalmos
Symptoms:
Heat intolerance
Thirst
Sweating
Weight loss despite adequate caloric intake
Amenorrhea
Tachycardia or atrial fibrillation
Congestive heart failure

28. PE: Laboratory Findings: Weight loss Decreased TSH Flushing
Warm and moist skin
Inappropriate sweating
Tachycardia
Widening of pulse pressure
Fine tremor
Muscle wasting
Hyperactive tendon reflexes
Pretibial myexedema
Gynecomastia
Audible bruit over the gland
Laboratory Findings:
Decreased TSH
Increased circulating T3/T4 levels
Increased circulating thyroid autoantibodies
Thyroid stimulating immunoglobulins (TSI)
Tyhroid stimulating antibodies (TSAb)
Radioactive iodine scan shows diffuse uptake through the gland of percent.

29. GRAVES’ OPHTHALMOPATHY
Thyroid-associated ophthalmopathy is one of the most typical symptoms of Graves' disease.
Thyroid eye disease is an inflammatory condition, which affects the orbital contents including the extraocular muscles and orbital fat. I
t is almost always associated with Graves' disease but may rarely be seen in Hashimoto's thyroiditis, primary hypothyroidism, or thyroid cancer.
The ocular manifestations that are relatively specific to Grave's disease include soft tissue inflammation, proptosis (protrusion of one or both globes of the eyes), corneal exposure, and optic nerve compression.
There are more general symptoms include lid retraction, lid lag, and a delay in the downward excursion of the upper eyelid, during downward gaze.
It is believed that fibroblasts in the orbital tissues may express the Thyroid Stimulating Hormone receptor (TSHr). This may explain why one autoantibody to the TSHr can cause disease in both the thyroid and the eyes.
Reference:

30. Classification of Graves Eye Disease
Mnemonic: "NO SPECS”
Class 0: No signs or symptoms
Class 1: Only signs (limited to upper lid retraction and stare, with or without lid lag)
Class 2: Soft tissue involvement (oedema of conjunctivae and lids, conjunctival injection, etc)
Class 3: Proptosis
Class 4: Extraocular muscle involvement (usually with diplopia)
Class 5: Corneal involvement (primarily due to lagophthalmos)
Class 6: Sight loss (due to optic nerve involvement)
Reference:

31. MANAGEMENT Medical: Propylthiouracil (PTU) Methimazole (Tapazole)
Carbimazole
Beta-blockers (Propanolol)

32. Relapse rate in 12-18 months
Risk for fetal goiter, hypothyroidism
No morbidity related after surgery
Treatment of choice for small goiters and pregnant patients (PTU)
Euthyroid state is achieved in 4-6 weeks

33. Radioactive Iodine Ease of treatment
Highly effective especially in diffuse goiters
No morbidity related to surgery
Treatment of choice for failed surgical management
The effect is seen in months
Standard dose = 10 mCl = 8500 cGy

34. Surgery Complete and permanent control of toxicity
Rapid control of symptoms
Removal of mass
Treatment of choice for huge goiters
Needs pre-operative preparation
Overall morbidity of 1-2%

35. Toxic Multinodular Goiter
Usually occur in individuals older than 50 years of age who often have a prior history of a nontoxic multinodular goiter
Over several years, enough thyroid nodules become autonomous to cause hyperthyroidism.
Similar to Graves’ disease, but symptoms and signs of hyperthyroidism are less severe and extrathyroidal manifestations are absent.
May present with atrial fibrillation or palpitations, tachycardia, nervousness, tremor or weight loss.
Low TSH, normal or minimally increased T4, elevated T3, T3>T4.

36. Toxic Multinodular Goiter
Thyroid scan – heterogenous uptake with multiple regions of increased and decreased uptake.
24hr uptake of radioiodine may not be increased.
Management
Antithyroid drugs + beta blockers – normalize thyroid function and address the clinical features of thyrotoxicosis, but often stimulates the growth of the goiter; spontaneous remission does not occur.
Radioiodine – treat areas of autonomy, decrease the mass of the goiter
A trial of radioiodine should be considered before subjecting patients to surgery.

37. Toxic Multinodular Goiter
Surgery
Definitive treatment of underlying thyrotoxicosis and goiter.
Subtotal thyroidectomy is the standard procedure.
Patients should be rendered euthyroid using antithyroid drugs before operation.

38. Toxic Adenoma A solitary, autonomously functioning thyroid nodule
Typically occurs in younger patients
(+) thyroid nodule with symptoms of hyperthyroidism
Size is at least 3cm before hyperthyroidism occurs.
Absent clinical features suggestive of Graves’ disease or other causes of thyrotoxicosis

39. Toxic Adenoma Thyroid scan – definitive diagnostic test
Focal uptake in the hyperfunctioning nodules
Diminished uptake in the remained of the gland
Suppression of the activity of the normal thyroid

40. Toxic Adenoma Radioiodine ablation – treatment of choice
131I is concentrated in the hyperfunctioning nodule with minimal uptake and damage to normal thyroid tissue.
Relatively large doses – correct thyrotoxicosis in about 75% of patients within 3 months.
Hypothyroidism occurs in <10% of patients over the next 5 years.

41. Toxic Adenoma Surgical resection Limited to enucleation of the adenoma
Lobectomy
Preservation of thyroid function
Low risk of hypoparathyroidism
Low risk of damage to the recurrent laryngeal nerve

42. Toxic Adenoma
Medical therapy using antithyroid drugs and beta blockers – normalize thyroid function but is not an optimal long term treatment
Ethanol injection under ultrasound guidance
Repeated injections – often >5 sessions
Reduce nodule size

43. Solitary Thyroid Nodule
Present in approximately 4 percent of the population
Pain is unusual. When present, it should raise suspicion for intrathyroidal hemorrhage in a benign nodule, thyroiditis, or malignancy.
History of hoarseness - may be secondary to malignant involvement of the recurrent laryngeal nerves
Risk factors for malignancy – exposure to ionizing radiation and family history of thyroid and other malignancies associated with thyroid cancer.

44. Solitary Thyroid Nodule
Mass moves with swallowing.
Hard, gritty of fixed nodules are more likely to be malignant.
Most are euthyroid.
If a patient with a nodule is found to be hyperthyroid, the risk of malignancy is approximately 1 percent.
FNAB – most important diagnostic test
Benign – 65% (includes cysts and colloid nodules)
Suspicious – 20%
Malignant – 5%
Nondiagnostic – 10%

45. Solitary Thyroid Nodule
Ultrasound
For detecting nonpalpable thyroid nodules
For differentiating solid from cystic nodules
For diagnosing suspicious nodules with microcalcifications
For identifying adjacent lymphadenopathy
CT and MRI – unnecessary in except for large, fixed, or substernal lesions.
123I or 99mTc – rarely necessary, unless evaluating patients for “hot” or autonomous thyroid nodules

46. Solitary Thyroid Nodule
Malignant tumors – generally treated by total or near- total thyroidectomy
Simple thyroid cysts - resolve with aspiration in approximately 75 percent of cases
Unilateral thyroid lobectomy - if the cyst persists after three attempts at aspiration
Lobectomy
For cysts >4 cm in diameter
For complex cysts with solid and cystic components

47. Solitary Thyroid Nodule
Colloid nodule – should be observed with serial ultrasound and Tg measurements
Repeat FNAB if nodule enlarges
L-thyroxine – in doses sufficient to maintain a serum TSH level between 0.1 and 1.0 μU/mL.
50% decrease in size
Thyroidectomy – if a nodule enlarges on TSH suppression, causes compressive symptoms, or for cosmetic reasons
Exceptions: Patient who has had previous irradiation of the thyroid gland or who has a family history of thyroid cancer.
In these patients total or near-total thyroidectomy is recommended.
High incidence of thyroid cancer (≥ 40%)
Decreased reliability of FNA biopsy

48. 4. How would you manage this patient now?

49. SYMPTOMATIC TREATMENT:
Goal: restoration of clinical and biochemical euthyroid state by omitting or reducing the dosage of medications and other measures as needed depending on clinical status.
ECG
Blood test: TSH, T3, T4 levels, monitored regularly
SYMPTOMATIC TREATMENT:
To control tachycardia, hypertension and atrial fibrillation: mg doses of propranolo Q 6hours; d
If beta blockers are contraindicated: Diazepam and/or chlorpromazine

50. RADIOACTIVE IODINE
ingestion of a radioactive iodine tablet (6-12 wks) which is then taken up by thyroid cells. These overactive cells are destroyed so that the thyroid can shrink in size and produce hormone at normal levels.
In patients with underlying heart disease and in elderly patients, it is desirable to treat with antithyroid drugs (methimazole) until the patient is euthyroid. The medication is then stopped for 5-7days before the appropriate dosage of 131I.
Although it is a safe treatment, most people become hypothyroid after radioactive iodine therapy and therefore require lifelong thyroid hormone replacement therapy.

51. THYROIDECTOMY
Now uncommonly performed; the surgeon removes most or all of the gland
Candidates for surgery: include pregnant hyperthyroid patients intolerant of anti-thyroid drugs, patients desiring definitive therapy without the use of radioactive iodine, children, and patients with very large or multinodular goiters.
Patients are treated with antithyroid drugs until euthyroid (about 6wks). In addition, days prior to surgery, they receive saturated solution of potassium iodide 5 drops BID, to diminish vascularity of the gland and simplify surgery
However, in cases of total removal of the thyroid gland, patient must take thyroid replacement pills for the rest of his or her life

52. NON-PHARMACOLOGICAL
High calorie diet in order to replace all the energy burned by the body in hyperthyroid state
Drink plenty of water and juices to replace all the fluid losses. Avoid or limit caffeinated drinks for such could produce anxiety.

53. Journals on Diagnosis and Treatment of Drug Induced Hyperthyroidism

54. Diagnosis
“Newly diagnosed thyrotoxicosis in hospitalized patients: clinical characteristics”
Rotman-Pikielny P et. Al

55. Background:
Thyrotoxicosis is often diagnosed in an outpatient setting. Most common symptoms include irritablility, heat intolerance ,palpitations and weakness
The prevalent symptoms in hospitalized patients with newly diagnosed thyrotoxicosis have not been fully characterized

56. Objective
To determine the clinical characteristics of patients with thyrotoxicosis newly diagnosed during hospitalization.

57. Design
Retrospective computer-based search was undertaken to detect patients that were hospitalized in our medical centre during , and discharged with thyrotoxicosis or thyroiditis primary diagnosis.

58. Results
Fifty-eight patients (36F/22M; mean age / years) were identified.
Weakness, weight loss and palpitations were the most common manifestations (50, 40 and 35%, respectively) and were predominantly present in patients with hyperthyroidism.
Sore throat was present in 41% of patients with thyroiditis.

59. Sinus tachycardia and atrial fibrillation occurred in 65. 5 and 15
Sinus tachycardia and atrial fibrillation occurred in 65.5 and 15.5% of the patients, more common in those with hyperthyroidism.
The diagnoses on discharge were Graves' disease, subacute thyroiditis and multinodular goiter in 39.7, 34.5 and 8.9%, respectively.

60. Conclusion
Weakness, weight loss and palpitations were the main symptoms in patients diagnosed with thyrotoxicosis during hospitalization.
Thyrotoxicosis should be included in the differential diagnosis when patients are admitted to the hospital with those symptoms.

61. Treatment
“Drug induced thyrotoxicosis: the surgical option” Lorberboym M., Schacter P. Background: Drug induced thyrotoxicosis is not uncommon, It may worsen life threatening arrythmias and become refractory to medical treatment

62. Summary
The Article talks about a near total thyroidectomy as valid alternative to medical therapy
The article pursues to promote near total thyroidectomy as an early management of the disease

63. Methods
The study included 12 patients 7 men and 5 women aged years of age with drug induced fulminant thyrotoxicosis
Drugs such as Iodine containing Amiodarone or IFN a treatment
Patients has adjunct medical therapy of an anti thyroid Propylthiouracil 1200 mg and a Beta receptor antagonist

64. Thyroid scan was performed in all patients using Tc-99m pertechnate

65. Results
4 patients did not respond to 3 months of medical therapy required surgical thyroidectomy due to unremitting thyrotoxicosis.
Near total thyroidectomy resulted into rapid correction of thyrotoxicosis enabling continuation of anti-arrythmic drugs
All patients recovered rapidly and remained well and euthyroid on thyroxine replacement therapy