Session 3 - Group Work Flashcards
1) A 29-year-old woman presents with a history of increased sweating and palpitations with weight loss of 7 kg over the last 2 years. On examination, she is nervous, agitated with an obvious diffuse, non-tender enlargement of her thyroid. Her resting pulse is 150/min. Her aunt has also suffered from “thyroid disease”.
On investigation, she has raised serum T3 of 4.8 nmol/ml (NR 0.8-2.4) and a T4 of 48 nmol/l (NR 9-23). Level of the thyroid-stimulating hormone was normal 0.4 mU/l (NR 0.5-5). A diagnosis of Graves’ disease (autoimmune thyrotoxicosis) was made.
a) - Describe the signs/symptoms suggesting a “thyroid” problem
Symptoms
- Weight loss (7kg over 2 yrs)
- Palpitations
- Tachycardia (HR 150 bpm)
- Sweating
Signs
- Raised T3 and T4
1) A 29-year-old woman presents with a history of increased sweating and palpitations with weight loss of 7 kg over the last 2 years. On examination, she is nervous, agitated with an obvious diffuse, non-tender enlargement of her thyroid. Her resting pulse is 150/min. Her aunt has also suffered from “thyroid disease”.
On investigation, she has raised serum T3 of 4.8 nmol/ml (NR 0.8-2.4) and a T4 of 48 nmol/l (NR 9-23). Level of the thyroid-stimulating hormone was normal 0.4 mU/l (NR 0.5-5). A diagnosis of Graves’ disease (autoimmune thyrotoxicosis) was made.
b) Describe the type of hypersensitivity reaction involved in the disease
Type 2
1) A 29-year-old woman presents with a history of increased sweating and palpitations with weight loss of 7 kg over the last 2 years. On examination, she is nervous, agitated with an obvious diffuse, non-tender enlargement of her thyroid. Her resting pulse is 150/min. Her aunt has also suffered from “thyroid disease”.
On investigation, she has raised serum T3 of 4.8 nmol/ml (NR 0.8-2.4) and a T4 of 48 nmol/l (NR 9-23). Level of the thyroid-stimulating hormone was normal 0.4 mU/l (NR 0.5-5). A diagnosis of Graves’ disease (autoimmune thyrotoxicosis) was made.
c) The patient also presents evidence of exophthalmos (bulging of the eyes out the eyeballs), which is a feature found in ~50% of patients with Graves’ disease. Explain for the immune mechanisms that are responsible for exophthalmos.
Inflammatory disease - proliferation of fibroblasts, increases deposition of CT in ECM; also adipocyte proliferation and differentiation. The eyes are also particularly sensitive to the cytokines produced as a result, so there is swelling there.
1) A 29-year-old woman presents with a history of increased sweating and palpitations with weight loss of 7 kg over the last 2 years. On examination, she is nervous, agitated with an obvious diffuse, non-tender enlargement of her thyroid. Her resting pulse is 150/min. Her aunt has also suffered from “thyroid disease”.
On investigation, she has raised serum T3 of 4.8 nmol/ml (NR 0.8-2.4) and a T4 of 48 nmol/l (NR 9-23). Level of the thyroid-stimulating hormone was normal 0.4 mU/l (NR 0.5-5). A diagnosis of Graves’ disease (autoimmune thyrotoxicosis) was made.
d) What treatment is available to treat patients with Graves’ disease.
Anti-thyroid drugs - carbimazole (inhibits thyroid peroxidase)
Radioactive-iodine therapy
Plasmapheresis
Surgery
1) A 29-year-old woman presents with a history of increased sweating and palpitations with weight loss of 7 kg over the last 2 years. On examination, she is nervous, agitated with an obvious diffuse, non-tender enlargement of her thyroid. Her resting pulse is 150/min. Her aunt has also suffered from “thyroid disease”.
On investigation, she has raised serum T3 of 4.8 nmol/ml (NR 0.8-2.4) and a T4 of 48 nmol/l (NR 9-23). Level of the thyroid-stimulating hormone was normal 0.4 mU/l (NR 0.5-5). A diagnosis of Graves’ disease (autoimmune thyrotoxicosis) was made.
e) The patient is currently pregnant. Is there any risk for the baby?
Yes
The risks to the baby from Graves’ disease are due to one of three possible mechanisms:
1) UNCONTROLLED MATERNAL HYPERTHYROIDISM: Uncontrolled maternal hyperthyroidism has been associated with fetal tachycardia (fast heart rate), small for gestational age babies, prematurity, stillbirths and possibly congenital malformations.This is another reason why it is important to treat hyperthyroidism in the mother.
2) EXTREMELY HIGH LEVELS OF THYROID STIMULATING IMMUNOGLOBLULINS (TSI): Graves’ disease is an autoimmune disorder caused by the production of antibodies that stimulate thyroid gland referred to as thyroid stimulating immunoglobulins (TSI). These antibodies do cross the placenta and can interact with the baby’s thyroid. Although uncommon (2-5% of cases of Graves’ disease in pregnancy), high levels of maternal TSI’s, have been known to cause fetal or neonatal hyperthyroidism. Fortunately, this typically only occurs when the mother’s TSI levels are very high (many times above normal). Measuring TSI in the mother with Graves’ disease is often done in the third trimester. In the mother with Graves’ disease requiring antithyroid drug therapy, fetal hyperthyroidism due to the mother’s TSI is rare, since the antithyroid drugs also cross the placenta. Of potentially more concern to the baby is the mother with prior treatment for Graves’ disease (for example radioactive iodine or surgery) who no longer requires antithyroid drugs. It is very important to tell your doctor if you have been treated for Graves’ Disease in the past so proper monitioring can be done to ensure the baby remains healthy during the pregnancy.
3) ANTI-THYROID DRUG THERAPY (ATD). Methimazole (Tapazole) or propylthiouracil (PTU) are the ATDs available in the United States for the treatment of hyperthyroidism (see Hyperthyroidism brochure). Both of these drugs cross the placenta and can potentially impair the baby’s thyroid function and cause fetal goiter. Historically, PTU has been the drug of choice for treatment of maternal hyperthyroidism, possibly because transplacental passage may be less than with Tapazole. However, recent studies suggest that both drugs are safe to use during pregnancy. It is recommended that the lowest possible dose of ATD be used to control maternal hyperthyroidism to minimize the development of hypothyroidism in the baby or neonate. Neither drug appears to increase the general risk of birth defects. Overall, the benefits to the baby of treating a mother with hyperthyroidism during pregnancy outweigh the risks if therapy is carefully monitored.
1) A 29-year-old woman presents with a history of increased sweating and palpitations with weight loss of 7 kg over the last 2 years. On examination, she is nervous, agitated with an obvious diffuse, non-tender enlargement of her thyroid. Her resting pulse is 150/min. Her aunt has also suffered from “thyroid disease”.
On investigation, she has raised serum T3 of 4.8 nmol/ml (NR 0.8-2.4) and a T4 of 48 nmol/l (NR 9-23). Level of the thyroid-stimulating hormone was normal 0.4 mU/l (NR 0.5-5). A diagnosis of Graves’ disease (autoimmune thyrotoxicosis) was made.
f) - Fill the table below with names of other endocrine diseases involving hypersensitivity reactions, their typical autoantigens, the immunological tissue damage and the physiological impact.
Disease/autoantigens/Targeted tissues/Physiological
impact
Hashimoto’s thyroiditis
Type 1 diabetes
Addison’s
disease
Disease/autoantigens/Targeted tissues/Physiological
impact
Hashimoto’s thyroiditis/thyroid peroxidase and thyroglobulin/thyroid/hyperthyroidism
Type 1 diabetes/pancreatic islet cells/pancreas/hyperglycaemia
Addison’s
disease/steroid 21 hydroxylase/adrenal cortex/adrenal insufficiency
1) A 29-year-old woman presents with a history of increased sweating and palpitations with weight loss of 7 kg over the last 2 years. On examination, she is nervous, agitated with an obvious diffuse, non-tender enlargement of her thyroid. Her resting pulse is 150/min. Her aunt has also suffered from “thyroid disease”.
On investigation, she has raised serum T3 of 4.8 nmol/ml (NR 0.8-2.4) and a T4 of 48 nmol/l (NR 9-23). Level of the thyroid-stimulating hormone was normal 0.4 mU/l (NR 0.5-5). A diagnosis of Graves’ disease (autoimmune thyrotoxicosis) was made.
g) Summarize the overall evidence implicating immunological mechanisms in the pathogenesis of Graves’ disease
TSI - binds to receptor on thyroid, stimulates release of T3 and T4, get an increase in sympathetic drive - as a result you get inflammatory reaction and cytokine infiltration e.g. scarring, fibrosis, and then as a result of the inflammation you get T cells into the thyroid, which causes further damage.
2) A 39-year old woman presented with a large, painless swelling in her neck. The enlargement had been a gradual process over 2 years. She had no other symptoms and felt generally well. On examination, her thyroid was diffusely enlarged and had a rubbery consistency. There was no sign of thyrotoxicosis. Thyroid function tests showed that she was euthyroid (normal functioning thyroid gland seen in ~75% of patients at presentation): T3 was 1.2 nml/l (NR0.8-2.4), T4 was 12 nmol/l (9-23) and TSH was 6.3 (0.4-5 mM/l).
a) Which symptoms would you expect in a patient with hypothyroidism?
- Weight gain
- Lethargy
- Loss of outer third of eyebrows
- Tiredness
- Cold intolerance
- Constipation
2) A 39-year old woman presented with a large, painless swelling in her neck. The enlargement had been a gradual process over 2 years. She had no other symptoms and felt generally well. On examination, her thyroid was diffusely enlarged and had a rubbery consistency. There was no sign of thyrotoxicosis. Thyroid function tests showed that she was euthyroid (normal functioning thyroid gland seen in ~75% of patients at presentation): T3 was 1.2 nml/l (NR0.8-2.4), T4 was 12 nmol/l (9-23) and TSH was 6.3 (0.4-5 mM/l).
b) A diagnosis of Hashimoto’s disease was raised. How would the serology confirm the diagnosis?
Anti-thyroid peroxidase
2) A 39-year old woman presented with a large, painless swelling in her neck. The enlargement had been a gradual process over 2 years. She had no other symptoms and felt generally well. On examination, her thyroid was diffusely enlarged and had a rubbery consistency. There was no sign of thyrotoxicosis. Thyroid function tests showed that she was euthyroid (normal functioning thyroid gland seen in ~75% of patients at presentation): T3 was 1.2 nml/l (NR0.8-2.4), T4 was 12 nmol/l (9-23) and TSH was 6.3 (0.4-5 mM/l).
c) Discuss the genetic factors associated with Hashimoto’s disease.
- Genetic associations with autoimmunity
8x increased risk if family member has it
30x increased risk if you have an identical twin
2) A 39-year old woman presented with a large, painless swelling in her neck. The enlargement had been a gradual process over 2 years. She had no other symptoms and felt generally well. On examination, her thyroid was diffusely enlarged and had a rubbery consistency. There was no sign of thyrotoxicosis. Thyroid function tests showed that she was euthyroid (normal functioning thyroid gland seen in ~75% of patients at presentation): T3 was 1.2 nml/l (NR0.8-2.4), T4 was 12 nmol/l (9-23) and TSH was 6.3 (0.4-5 mM/l).
d) Fine Needle Biopsy of the thyroid gland was performed. Which cells from the adaptive immunity are expected to be found in the thyroid gland tissue?
Infiltration of T cells
2) A 39-year old woman presented with a large, painless swelling in her neck. The enlargement had been a gradual process over 2 years. She had no other symptoms and felt generally well. On examination, her thyroid was diffusely enlarged and had a rubbery consistency. There was no sign of thyrotoxicosis. Thyroid function tests showed that she was euthyroid (normal functioning thyroid gland seen in ~75% of patients at presentation): T3 was 1.2 nml/l (NR0.8-2.4), T4 was 12 nmol/l (9-23) and TSH was 6.3 (0.4-5 mM/l).
e) Around 50% of patients eventually become hypothyroid due to the destruction of the thyroid gland. Describe the type of hypersensitivity reactions causing the disease.
Type 4 hypersensitivity reactions
2) A 39-year old woman presented with a large, painless swelling in her neck. The enlargement had been a gradual process over 2 years. She had no other symptoms and felt generally well. On examination, her thyroid was diffusely enlarged and had a rubbery consistency. There was no sign of thyrotoxicosis. Thyroid function tests showed that she was euthyroid (normal functioning thyroid gland seen in ~75% of patients at presentation): T3 was 1.2 nml/l (NR0.8-2.4), T4 was 12 nmol/l (9-23) and TSH was 6.3 (0.4-5 mM/l).
f) Describe the treatment for hypothyroidism and how it is monitored.
Replacement therapy
Thyroxine - then monitor TSH
2) A 39-year old woman presented with a large, painless swelling in her neck. The enlargement had been a gradual process over 2 years. She had no other symptoms and felt generally well. On examination, her thyroid was diffusely enlarged and had a rubbery consistency. There was no sign of thyrotoxicosis. Thyroid function tests showed that she was euthyroid (normal functioning thyroid gland seen in ~75% of patients at presentation): T3 was 1.2 nml/l (NR0.8-2.4), T4 was 12 nmol/l (9-23) and TSH was 6.3 (0.4-5 mM/l).
g) Summarize the evidence for an autoimmune pathogenesis in Hashimoto’s disease.
x
3) Thyroid Gland review
It is worth reviewing the basic information on the Thyroid gland. You may simple look up the lecture from MEH Session 7 or you can write the information below.
a) Regulation of thyroid hormone secretion: Draw a diagram showing the regulation of thyroid hormone secretion from the Hypothalamus to the target tissue
x
