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Q: A 70 y.o. man is brought to ER by his nephew because he was found poorly responsive at home. The nephew had not checked on the patient for two weeks. The patient lives alone and has been noted by his nephew to be more confused and less active over the past few months.
The nephew was uncertain about the patient's past medical history. He recalls that the patient takes several pills per day for some 'heart issues,' blood pressure, and headaches.
He also recalls that the patient was seen in ER recently for muscle pains and was given opioid analgesics.
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2. Objectives
* How to evaluate a patient with thyroid
disease?
* Hypothyroidism and Hyperthyroidism: causes,
pathogenesis, diagnosis and treatment.
* Other thyroid disorders.
3. Patients with thyroid disease
Thyroid enlargement (goiter): diffuse or nodular
Symptoms of hypothyroidism
Symptoms of hyperthyroidism
Complications of a specific form of hyperthyroidism-
Graves’ disease-which may present with:
- Striking prominence of the eyes (exophthalmos)
- Thickening of the skin over the lower leg (thyroid
dermopathy)
4. History
Exposure to ionizing radiation
Iodide ingestion:
- Kelp
- Iodide-containing cough preparation
- IV Iodide-containing contrast media
Lithium carbonate
Residence in an area of low dietary iodide
5. History
Family history
- Thyroid disease
- Immunologic disorders:
* Diabetes
* Rheumatoid disease
* Pernicious anemia
* Alopecia
* Vitiligo
* Myasthenia gravis
* MEN 2A
6. Physical examination
Observe the neck, especially as the patient
swallows
Examine from the front, rotating the gland
slightly with one thumb while palpating the
other lobe with the other thumb
Examine from behind, using three fingers and
the same technique
Determine the size of the thyroid lobes,
consistency, presence of nodules
8. Causes
Primary:
1. Hashimoto’s thyroiditis:
- With goiter
- “Idiopathic” thyroid atrophy, presumably end-stage autoimmune thyroid
disease, following either Hashimoto’s thyroiditis or Graves’ disease
- Neonatal hypothyroidism due to placental transmission of TSH-R blocking
antibodies
2. Radioactive iodine therapy for Graves’ disease
3. Subtotal thyroidectomy for Graves’ disease or nodular goiter
4. Excessive iodine intake (kelp, radiocontrast dyes)
5. Subacute thyroiditis
6. Iodide deficiency
7. Other goitrogens such as lithium, amiodarone, antithyroid drug therapy
8. Inborn errors of thyroid hormone synthesis
9. Causes
Secondary
- Hypopituitarism due to:
a- Pituitary adenoma
b- pituitary ablative therapy
c- pituitary destruction
Tertiary
- Hypothalamic dysfunction (rare)
Peripheral resistance of the action of thyroid
hormone
10. Pathogenesis
Thyroid hormone deficiency affects every
tissue in the body, so that the symptoms are
multiple
Accumulation of glycosaminoglycans-mostly
hyaluronic acid- in interstitial tissues
Increase capillary permeability to albumin
Interstitial edema (skin, heart muscle, striated
muscle)
11.
12. Clinical presentations and
findings
Adults
- Common feature: easy fatigability, coldness, weight gain, constipation,
menstrual irregularities, and muscle cramps.
- Physical findings: cool rough dry skin, puffy face and hands, hoarse
husky voice, and slow reflexes, yellowish skin discoloration.
- Cardiovascular:
Bradycardia
Decreased cardiac output
Low voltage ECG
Cardiomegaly
Pericardial effusion
- Pulmonary function
Shallow and slow respiration
Respiratory failure
13. Clinical presentations and
findings
Adults (cont’)
- GI:
Chronic constipation
Ileus
- Renal function:
Impaired GFR
Water intoxication
- Anemia:
Impaired hemoglobin synthesis
Iron deficiency
Folate deficiency
Pernicious anemia, with B12 deficient megaloblastic anemia
15. Diagnosis
Low serum FT4
Elevated serum TSH
Thyroid antibodies
TRH stimulation test
16. Individual and median values of thyroid function tests
in patients with various grades of
hypothyroidism. Discontinuous horizontal lines
represent upper limit (TSH) and lower limit (FT4,T3)
of the normal reference ranges. Reproduced with
permission from Ord WM: On myxedema, a term
proposed to be applied to an essential condition in
the "cretinoid" affection occasionally observed in
middle-aged women. Medico-Chir Trans 1878; 61:
57.
17. Complications
1- Myxedema coma
- The end stage of untreated hypothyroidism
- Progressive weakness, stupor, hypothermia, hypoventilation,
hypoglycemia, hyponatremia, water intoxication, shock, and death.
- Associate illnesses and precipitating factors: pneumonia, MI, cerebral
thrombosis, GI bleeding, ileus, excessive fluid administration, and
administration of sedatives and narcotics.
- Three main issues: CO2 retention and hypoxia, fluid and electrolyte
imbalance, and hypothermia.
2- Myxedema and heart disease
3- Hypothyroidism and neuropsychiatric
disease
18. Treatment
A- Hypothyroidism
- Levothyroxine (T4).
- Follow serum Free T4 and TSH
- Take dose in AM
- Do blood test fasting before taking the daily dose
- Adults: 1.7 ug/kg/d, but lower in elderly (1.6 ug/kg/d)
- For TSH suppression (nodular goiters or cancer): 2.2 ug/kg/d
- Increase dose of T4 in malabsorptive states or concurrent
administration of aluminum preparations, cholestyramine,
calcium, or iron compounds
- Increase dose of T4 in pregnancy and lactation
- The t1/2 of levothyroxine is 7 days
19. Treatment
B- Myxedema coma
- Acute medical emergency
- Monitor blood gases
- Patient may need intubation and mechanical ventilation
- Treat associated medical problems
- Avoid excessive hydration
- Asses adrenal function and treat if needed
- In pituitary myxedema, glucocorticoid replacement is essential
- IV levothyroxine: loading 300-400 ug, daily maintenance 50 ug
- Be cautious in patients with coronary artery disease
- Active rewarming of the body in contraindicated
20. Recommendations for the treatment of myxedema coma
• hypothyroidism
large initial intravenous dose of 300-500 µg
T4; if no response within 48 hours, add T3
• hypocortisolemia
intravenous hydrocortisone 200-400 mg
daily
• hypoventilation
don’t delay intubation and mechanical
ventilation too long
• hypothermia blankets, no active rewarming
• hyponatremia mild fluid restriction
• hypotension
cautious volume expansion with crystalloid
or whole blood
• hypoglycemia glucose administration
• precipitating event
identification and elimination by specific
treatment (liberal use of antibiotics)
21. Treatment
C- Myxedema with heart disease
- Start treatment slowly in long standing hypothyroidism and in elderly patients
particularly those with known cardiovascular disease
- 25 ug/d x 2 weeks, increase by 25 ug every 2 weeks until a daily dose of 100-
125 ug is reached
22. Treatment
Toxic effects of levothyroxine therapy
- No allergy has been reported to pure levothyroxine
- If FT4 and TSH are followed and T4 dose is adjusted, no side effects are
reported
- If FT4 is higher than normal: hyperthyroidism symptoms may occur:
Cardiac symptoms
Osteopenia and osteoporosis
24. Definitions
Thyrotoxicosis: is the clinical syndrome that
results when tissues are exposed to high
levels of circulating thyroid hormone
Hyperthyroidism: is the hyperactivity of the
thyroid gland
26. Diffuse Toxic Goiter
(Graves’ disease)
Most common form of thyrotoxicosis
Females > Males
Features:
- Thyrotoxicosis
- Goiter
- Orbitopathy (exophthalmos)
- Dermopathy (pretibial myxedema)
27. Etiology
Autoimmune disease of unknown cause
There is a strong familial predisposition
Peak incidence in the 20- to 40- year age
group
28. Pathogenesis
Local viral infection inflammatory reaction
leading to the production of IFN-g and other
cytokines by non-thyroid-specific infiltrating immune
cells
will induce the expression of HLA class II molecules on
the surface of thyroid follicular cells.
Subsequently, thyroid specific T-cells will recognize
the antigen presented on the HLA class II molecules
and will be activated
37. Figure 6-6. Thyroid Scans.
a. Normal thyroid imaged with 123I.
b. Cold nodule in the right lobe imaged by
99mTc.
c. Elderly woman with obvious multinodular
goiter and the corresponding radioiodide
scan on the right.
50. History
Goiter
Fist described in China in 2700 BC
Thyroid Function
Da Vinci – thyroid is designed to fill empty spaces in the neck
Parry – thyroid works as a buffer to protect the brain from
surges in blood flow
51. Surgical advances
500 AD
First goiter excision in Baghdad.
Procedure: unknown
1200’s AD
Advancements in goiter procedures included applying hot irons through
the skin and slowly withdrawing them at right angles.
Most died from hemorrhage or sepsis.
1646 AD
Wilhelm Fabricus performed a thyroidectomy with standard surgical
scalpels.
The 10 y/o girl died, and he was imprisoned
1808 AD
Guillaume Dupuytren performed a total thyroidectomy.
The patient died postoperatively of “shock”
52. Surgical advances
1866
“If a surgeon should be so foolhardy as to undertake it
[thyroidectomy] … every step of the way will be
environed with difficulty, every stroke of his knife will
be followed by a torrent of blood, and lucky will it be
for him if his victim lives long enough to enable him to
finish his horrid butchery.”
– Samuel David Gross
53. Surgical advances
1883
Kocher’s performs a retrospective review
5000 career thyroidectomies
Mortality rates decreased
40% in 1850 (pre-Kocher & Bilroth)
12.6% in 1870’s (Kocher begins practice)
0.2% in 1898 (end of Kocher’s career)
Many patients developed cretinism or myxedema
His conclusions ….
54. Surgical advances
In presentation to the German Surgical
Congress …
“ …the thyroid gland in fact had a function….”
- Theodor Kocher, 1883
55. Wolff-Chaikoff Effect
Increasing doses of I-
increase hormone synthesis
initially
Higher doses cause
cessation of hormone
formation.
This effect is countered by
the Iodide leak from normal
thyroid tissue.
Patients with autoimmune
thyroiditis may fail to adapt
and become hypothyroid.
56. Jod-Basedow Effect
Opposite of the Wolff-Chaikoff effect
Excessive iodine loads induce hyperthyroidism
Observed in hyperthyroid disease processes
Graves’ disease
Toxic multinodular goiter
Toxic adenoma
This effect may lead to symptomatic thyrotoxicosis in
patients who receive large iodine doses from
Dietary changes
Contrast administration
Iodine containing medication (Amiodarone)