Thyroid Disease: Diagnosis and Management

1
Thyroid DiseaseDiagnosis and Management

• Internal Medicine Resident Lecture Series
• Michael Pascolini D.O.
• 8/18/2004

2
Goal

• The residents will understand how to diagnose and
  manage thyroid disease

3
Objectives

• The residents will
• understand the basic hormonal actions of the
  thyroid gland
• evaluate and diagnose a patient with thyroid
  disease using clinical skills and lab work
• understand the four different types of Malignant
  thyroid tumors

4
Question 1

• In X-linked TBG deficiency, the TSH level is
• A. increased
• B. decreased
• C. normal

5
Thyroid Axis
Dopamine Glucocorticoids Somatostatin
Hypothalamus
TRH
Pituitary
TSH
Thyroid
T3 and T4
6
Thyroid Axis

• Thyroid hormones (T3 and T4) are the dominant
  regulator of TSH TRH production
• TSH production
• pulsatile diurnal (highest levels at night)
• long plasma 1/2 life (50 min)

7
Iodine

• Iodine transport is a critical first step in
  thyroid hormone synthesis
• Normal thyroid extracts 10-25 radioactive iodine
  trace over 24 hrs.
• Thyroid of Graves disease can extract 70-90
• Areas of iodine deficiency have increased
  incidence of Goiter
• Oversupply of iodine is associated with increased
  incidence of autoimmune thyroid disease
• Decreased iodine increases thyroid bloodflow
• Excess iodine inhibits thyroid iodide
  organification (Wolff-Chaikoff effect)

8
Thyroid hormones

• T4 is secreted 20x in excess of T3 from thyroid
  gland
• both are bound to plasma proteins
  thyroxine-binding thyroglobulin(TBG),
  transthyretin (TTR) and Albumin (99.98 T4 and
  99.7 T3)
• Free T3 gt Free T4 (only free hormone is available
  to tissues)

9
Thyroid hormones

• Homeostatic mechanisms maintain normal
  concentration of free hormones
• X-linked TBG deficiency - There are low levels of
  total T3 T4, however free hormone levels are
  normal.
• patients are euthyroid, TSH levels are normal
• TBG are increased by estrogen (pregnancy,
  estrogen birth control pills) TBG, total T3 T4
  are increased. Free T3 and T4 are normal.
• Do not try to normalize the total hormone levels

10
Question 1

• In X-linked TBG deficiency, the TSH level is
• A. increased
• B. decreased
• C. normal

11
Question 1

• In X-linked TBG deficiency, the TSH level is
• A. increased
• B. decreased
• C. normal

12
Question 2

• Which of the following can cause a decreased TSH
  level?
• A. severe non thyroid illness
• B. medications (increased levels of dopamine and
  glucocorticoids)
• C. TSH secreting pituitary tumor
• D. Thyroid hormone resistance (increased free T4
  T3 with normal TSH)

13
Physical Exam

• Extrathyroid features Opthalmopathy and
  Dermopathy
• Inspect pt from front and side
• Palpate thyroid from behind pt
• note tenderness, fixation, nodularity, masses
• Bruit over gland suggests increased vascularity
  (hyperthyroidism)

14
Physical Exam
15
Physical Exam

• If low boarders are not clearly felt, pt may have
  retrosternal goiter
• Venous distention, difficulty breathing,
  especially when arms are raised (Pembertons
  sign)
• Central Masses - have pt stick out tongue,
  thyroglossal cysts will move upward
• Asses lymphadenopathy in supraclavicular and
  cervical regions

16
Lab Eval

• First determine TSH level
• normal TSH level excludes primary abnormalities
  of thyroid function, with rare exceptions
• Abnormal TSH, next get a free T4 and T3 resin
  uptake tests
• Resin uptake test - compares amount of T3 bound
  to Resin as opposed to unoccupied thyroid hormone
  binding proteins
• uptake increased when proteins are low or Thyroid
  hormone levels are increased

17
Lab Eval

• TSH as screening test may be misleading
  (especially without Free T4)
• Increased TSH level
• severe non thyroid illness
• TSH secreting pituitary tumor
• Thyroid hormone resistance (increased free T4
  T3 with normal TSH)
• Artifact
• Decreased TSH level
• 1st trimester of pregnancy (2o hCG secretion)
• Treatment of hyperthyroidism (suppression lasts
  several weeks)
• medications (increased levels of dopamine and
  glucocorticoids)
• TSH should not be used to assess a patient with
  known pituitary disease.

18
Hypothyroidism - signs and symptoms (decreasing
order of frequency)

• Signs
• Dry coarse skin
• Puffy face, hands and feet
• Diffuse alopecia
• Bradycardia
• Peripheral edema
• Delayed tendon reflex relaxation
• Carpal tunnel syndrome
• Serous cavity effusion

• Symptoms
• Tiredness, weakness
• Feeling cold
• Difficulty concentrating and poor memory
• Constipation
• Weight gain with poor apatite
• Dyspnea
• Hoarse voice
• Menorrhagia
• Parasthesias
• Impaired hearing

19
Hypothyroidism

• increased TSH and a decreased free T4
• Congenital
• Autoimmune
• Iatrogenic

20
Hypothyroidism

• Congenital
• 1 in 3000-4000 newborns
• lt10 are diagnosed with clinical features
• prolonged jaundice, feeding problems, hypotonia,
  enlarged tongue, delayed bone maturation.
• permanent neurological damage could occur if
  treatment is delayed
• Treatment is levothyroxine at 10-15 mcg/kg/day,
  monitoring effects by TSH levels

21
Hypothyroidism

• Autoimmune
• may be associated with goiter (Hashimotos) or
  minimal residual thyroid tissue (atrophic
  thyroiditis), later in the disease.
• patients present with typical signs and symptoms

22
Hypothyroidism

• Iatrogenic
• may be caused by radioiodide treatment (in the
  1st 3-4 months after treatment)

23
Hypothyroidism

• Treatment
• Start daily replacement dose of levothyroxine at
  1.5 mcg/kg of body weight
• adjust the dose based on TSH levels
• once replacement is achieved, annual TSH are
  recommended to follow

24
Thyrotoxicosis - signs and symptoms (decreasing
order of frequency)

• Signs
• Tachycardia A-fib in the elderly
• Tremor
• Goiter
• Warm, moist skin
• Muscle weakness, proximal myopathy
• Lid retraction or lag
• Gynecomastia

• Symptoms
• Hyperactivity, irritability, dysphoria
• Heat intolerance and sweating
• Palpitations
• Fatigue and weakness
• Weight loss with increased apatite
• Diarrhea
• Polyuria
• Oligomenorrhea

25
Thyrotoxicosis

• Thyrotoxicosis - the state of thyroid hormone
  excess
• Hyperthyroidism - result of excessive thyroid
  function
• Labs Decreased TSH and increased free T3 T4
• Etiologies
• Graves disease
• Thyroiditis
• Toxic Adenoma

26
Thyrotoxicosis

• Graves disease
• 60-80 of thyrotoxicosis, depending on iodine
  intake (increased intake increased prevalence)
• Diagnosis can be excluded if TSH is normal
• clinical features worsen without treatment
  mortality 10-30

27
Thyrotoxicosis

• Graves disease
• Treatment goal is to reduce thyroid hormone
  synthesis using antithyroid drugs
• Thionamides
• Propylthiouracil 100-200mg q 6-8 hours
• Carbimazole 10-20 mg BID or TID
• Methimazole 10-20 mg BID or TID

28
Thyrotoxicosis

• Thyroiditis
• Acute
• pt presents in thyroid pain
• infection of thyroid, rare, usually secondary to
  presence of piriform sinus
• Treatment guided by Gram stain and culture of FNA
  biopsy
• Subacute (deQuervains thyroiditis)
• many viruses implicated as cause peak incidence
  30-50 yrs FgtM
• Treat with relatively large doses of Aspirin or
  other NSAIDs.(600mg q4-6 hrs)

29
Thyrotoxicosis

• Thyroiditis
• Silent (painless thyroiditis)
• usually pts have underlying autoimmune thyroid
  disease
• clinical course same as subacute thyroiditis
  without the pain
• glucocorticoids are not indicated
• Propranolol may be used to treat sever
  thyrotoxicosis

30
Thyrotoxicosis

• Toxic adenoma
• autonomously functioning thyroid nodule
• hypersecretion of T4 and T3 leads to
  thyrotoxicosis
• etiology related to iodine deficiency
• Always greater than 3cm in diameter
• Labs decreased TSH and marked elevation of T3
  levels, borderline elevation of T4
• Almost never malignant
• May treat with antithyroid drugs but if size
  continues to increase, then surgery or I-131
  therapy

31
Sick Euthyroid Syndrome

• Any acute, severe illness can cause abnormalities
  in TSH of thyroid hormone levels in the absence
  of underlying disease. These measurements can be
  misleading
• Common pattern Decreased Total and Free T3 with
  normal levels of T4 and TSH

32
Amiodarone effects on Thyroid

• Amiodarone is structurally related to thyroid
  hormone and contains 39 iodine by weight
• increased iodine levels for gt6 months after
  discontinuation of drug
• Multiple effects on thyroid function
• acute, transient changes in thyroid function
• hypothyroidism in susceptible patients with
  increased iodine
• thyrotoxicosis, possibly by induction of
  autoimmune Graves disease

33
Question 2

• Which of the following can cause a decreased TSH
  level?
• A. severe non thyroid illness
• B. medications (increased levels of dopamine and
  glucocorticoids)
• C. TSH secreting pituitary tumor
• D. Thyroid hormone resistance (increased free T4
  T3 with normal TSH)

34
Question 2

• Which of the following can cause a decreased TSH
  level?
• A. severe non thyroid illness
• B. medications (increased levels of dopamine and
  glucocorticoids)
• C. TSH secreting pituitary tumor
• D. Thyroid hormone resistance (increased free T4
  T3 with normal TSH)

35
Question 3

• Which of the following malignant tumors has the
  poorest prognosis?
• A. Anaplastic carcinoma
• B. Follicular (well-differentiated thyroid
  carcinomas)
• C. Papillary
• D. Medullary thyroid carcinoma

36
Benign lesions

• Can be categorized into
• nontoxic - diffuse and multinodular goiter
• toxic - toxic multinodular goiter, solitary toxic
  adenoma, and diffuse toxic goiter (Graves
  disease)
• inflammatory - Thyroiditis acute, subacute and
  chronic
• Benign thyroid diseases are significant to the
  surgeon because
• mechanical constraint on the upper aerodigestive
  structures
• its not possible to rule out carcinoma within a
  nodular lesion of the thyroid gland

37
Malignant tumors

• Primary epithelial tumors, they account for 1.5
  of all cancer in the US
• Papillary
• Follicular (well-differentiated thyroid
  carcinomas)
• Medullary thyroid carcinoma
• Anaplastic carcinoma

38
Papillary Adenocarcinomas

• 80 of all thyroid carcinomas
• incidence in the 3rd and 4th decade
• both lobes involved in 80 of the cases often
  multicentric
• tumor spreads by regional lymphatics to
  paratracheal or lateral cervical lymph nodes
• locoregional metastasis is high from 37-65
• 5-year survival rates range from 70-95 with
  mortality of 10-20 over 10-20 year period
• significant mortality occurs from intrathyroidal
  lesions gt 5cm in diameter or extracapsular spread

39
Follicular Carcinomas

• 10 of all thyroid cancers
• more prevalent in areas of endemic goiter
• occurs exclusively in patients older than 40
  years
• Multicentricity is uncommon as is lymph node
  metastasis
• tumor spreads by angioinvasion distant mets to
  lungs or bone in 65of patients
• 5-year survival rate is about 70, decreasing to
  40 at 10 years.
• if distant mets present, 5-year survival is 20

40
Medullary Thyroid Carcinoma

• 5-7 of thyroid carcinomas
• originate from parafollicular cells (neural crest
  cells)
• calcified areas in the thyroid is a radiological
  feature of this tumor
• 60-80 are sporadic cases10-40 are familial.
• sporadic case is unilateral familial cases are
  bilateral
• Familial cases occur in the MEN syndrome type II
• better prognosis than the sporadic cases
• 5- and 10-year survival rates range from 88 and
  78, respectively
• cervical lymph node mets affects 10 year rate
  down to 46

41
Anaplastic Carcinoma

• one of the most lethal carcinomas 1-5 of
  thyroid malignancies
• mainly affects patients older than 65 years.
• only small-cell type responds to radiation
  therapy
• Approximately 10 of patients will survive 1
  year.
• Average duration of survival after diagnosis is
  3-6 months
• Effective treatment is rarely feasible.

42
Thyroid Ultrasound

• Can differentiate cystic from solid thyroid
  nodules in gt80 cases
• used increasingly in the diagnosis of thyroid
  disease
• 10MHz instruments with detection of nodules gt3mm
• Can also be used to monitor nodular sizes, guide
  FNA biopsies and aspiration of cystic lesions

43
Thyroid scanning

• Radioisotopes of iodine can be used to trace the
  fractional uptake into the gland
• Graves disease - shows and enlarged thyroid with
  homogenous tracer uptake
• Toxic Adenoma - shows areas of increased uptake
  with suppressed tracer uptake in remainder of
  gland
• Toxic Multinodular goiter - Enlarged gland with
  multiple areas of increased and decreased uptake

44
Thyroid scanning

• Subacute thyroiditis - very low uptake due to
  cell damage
• Thyrotoxicosis factitia (self-administration of
  thyroid hormone) - low uptake
• Cold nodules are usually benign, but have 5-10
  chance of being malignant
• Hot nodules are almost never malignant
• Scans are also used to follow up on thyroid
  cancer. Uptake in the thyroid bed after surgery
  may show metastatic thyroid cancer deposits.

45
Thyroid scanning
46
Fine Needle Aspiration

• most accurate preop diagnostic modality for
  evaluation of thyroid nodules
• Has decreased the need for thyroid surgeries by
  50 and increased yield of thyroid malignancies
  by 50
• reports classified as benign, indeterminate or
  malignant
• fewer than 5 false-positives on malignancies

47
Indications for Operation
Scan
Needle Bx
Cystic
Solid
Rapid recurrence
disappearance
Neg
Pos. or ?
Surgery
Surgery
growth or failure to suppress
Suppression cont.
Surgery
48
Treatment

• Thyroidectomy
• hemithyroidectomy - half of the thyroid is
  removed, parathyroids preserved
• total thyroidectomy - entire thyroid is removed,
  parathyroids preserved

49
Complications of Surgery

• complication rate is low
• reported complications with surgery
• transient hypocalcemia (7.1)
• permanent hypocalcemia (0.4)
• Vocal cord paralysis (1.2)

50
Further management

• 131I thyroid ablation and treatment should be
  coordinated with the surgical approach
• ablation is much more effective when there is
  less normal thyroid tissue in the thyroid bed.
• Patient is kept on thyroid treatment for a few
  weeks post op, then withdrawn.
• TSH rise correlates to the amount of normal
  tissue left.
• The residual tissue is then ablated with 131I

51
Further management

• An initial whole-body scan should be performed
  about 6 months after surgery and thyroid ablation
  for more residual tissue.
• if positive another larger ablative dose is given
• if negative and thyroglobulin (Tg) levels are
  low, a repeat scan should be done 1 year later
• if negative again, then patient can be managed
  with suppressive therapy and Tg levels every 6 to
  12 months

52
Question 3

• Which of the following malignant tumors has the
  poorest prognosis?
• A. Anaplastic carcinoma
• B. Follicular (well-differentiated thyroid
  carcinomas)
• C. Papillary
• D. Medullary thyroid carcinoma

53
Question 3

• Which of the following malignant tumors has the
  poorest prognosis?
• A. Anaplastic carcinoma
• B. Follicular (well-differentiated thyroid
  carcinomas)
• C. Papillary
• D. Medullary thyroid carcinoma