Thyroid Disease Flashcards
If a patient has had unintentional weight loss, what additional questions do you need to ask?
- GI symptoms (anorexia, abdo pain, diarrhea, symptoms of inflammatory bowel disease, celiac disease, peptic ulcer)
- Symptoms of depression (low mood, loss of interest, sleep disturbance)
- Symptoms of eating disorder (decreased food intake, self-induced vomiting, over-exercise)
- Polyuria + polydipsia (T1 diabetes)
- Drug use (alcohol, cocaine, amphetamines, cannabis)
- Night sweats/fever (lymphoma, TB, HIV)
What physical signs would point towards hyperthyroidism?
- Agitation
- Tremor
- Onycholysis (detachment of nail from nail bed)
- Acropachy (soft tissue swelling + clubbing of hands)
- Conjunctival oedema
- Opthalmoplegia
- Pretibial myxoedema
- Proximal myopathy
- Hyperreflexia
What thyroid test results are consistent with primary hyperthyroidism?
Elevated free T4 and free T3 with suppressed TSH
Why is TSH low in primary hyperthyroidism?
Production of TSH is regulated by feedback from circulating free thyroid hormone concentrations. Elevated levels of free T4 and free T3 therefore suppress TSH levels
Name 4 target tissues of T3 and T4
- Heart
- Liver
- Bone
- CNS
What are the 3 commonest causes of hyperthyroidism?
- Grave’s Disease
- 60-80% of cases of hyperthyroidism. Due to an autoimmune process resulting in the production of stimulating antibodies to the thyroid TSH receptor. Mimic the effects of TSH and stimulate thyroid gland to produce thyroid hormones. In up to 50% of these patients opthalmopathy occurs. This is an autoimmune disease of the rtetroorbital tissues and is thought to be related to the activation of T cells stimulated by TSH receptor antigen - Toxic multi nodular goitre
- Occurs when 2+ autonomously functioning nodules secrete thyroid hormones. - Solitary toxic adenoma
- Account for up to 5% of cases of hyperthyroidism
Which of the following clinical features are only found in hyperthyroidism due to Grave’s Disease?
- Pretibial myxoedema
- Thyroid acropachy
- Opthalmoplegia
- Exopthalmos
What is the potentially serious side effect of carbimazole?
What advice should a doctor give their patient as a result?
- Neutropenia
- Agranulocytosis
Report signs of infection especially sore throat. Dr would need to check FBC if there are signs/symptoms of infection + stop treatment with carbimazole if WBC count is low.
How should thyroid disorder treatment be amended during pregnancy?
Hyperthyroidism:
- May develop short-term hyperthyroidism (gestational thyrotoxicosis) in the early weeks of pregnancy which settles without the need for drug therapy
- Baby has risk of developing temporary hyperthyroidism if patient has had Grave’s Disease
- Propylthiouracil is treatment of choice during pregnancy
Hypothyroidism:
- Levothyroxine dose should be increased by 25-50mcg daily once patient is pregnant
- Can safely breastfeed on levothyroxine
- Heel-prick test of baby will determine whether they have hypothyroidism
What is the mechanism of neonatal hyperthyroidism?
Thyroid stimulating antibodies (in Grave’s Disease) can cross the placenta + stimulate the thyroid gland of the fetus
What are the 6 main roles of thyroid hormones in metabolism?
Remember their role is to increase metabolic rate…
- Oxygen consumption, increased glucose absorption, gluconeogenesis, glycogenolysis, lipolysis, protein synthesis, basal metabolic rate
- Cardiac output
- Heart rate + increased respiratory rate
- Growth of bones + muscle
- Brain development
- Sexual maturation
Explain the hypothalamic-pituitary-thyroid axis
The hypothalamus secretes thyroid-releasing hormone (TRH) which stimulates the release of TSH from the pituitary. This stimulates the thyroid to release T4 and T3
They both go into the circulation and T4 is deionized into T3 which acts by way of negative feedback to inhibit the further release of TRH and TSH when in excess.
T4 and T3 both also go on to target tissues: heart, liver, bone, and CNS
Describe the thyroid gland?
Soft gland in the lower neck.
Anterior to trachea below thyroid cartilage of the larynx
Makes tyrosine (T4) and triiodothyronine (T3)
2 lobes + isthmus
Normally impalpable
Describe the histology of the thyroid
- Follicles filled with colloid (reservoir where the hormones are made)
- Lined with cuboidal epithelium - single layer of thyroid follicular cells - which produce thyroglobulin (precursor for thyroid hormones)
- Interspersed C-cells within follicles produce calcitonin (which regulates Ca2+ and phosphate levels in the blood, opposing the action of parathyroid hormone)
How is thyroid hormone synthesized?
- Thyroid follicular cells (TFC) make thyroglobulin under control of TSH activated by TSHR and secrete it into the colloid.
- Iodine is trapped by the TFC and transported into the colloid.
- Thyroglobulin, produced from the ER is packaged in the golgi and moves to the colloid, to provide sources of tyrosines
- TPO (thyroid peroxidase) on the luminal membrane of TFCs iodinates 2 tyrosines together = tyrosine residue which is then cleared from the TFC
- Thyroglobulin is endocytosed back into the TFC
- T3 and T4 deionized and the go into the blood. They are both lipid hormones (can diffuse easily) and must be protein-bound to travel + have effects on peripheral tissues
- T4 deiodinizes into T3 which is an ACTIVE intracellular hormone (T4 is a prohormone)
- T3 acts on nuclear hormone receptors (Retinoic x-receptor + thyroid hormone receptor) -> creates new mRNA -> promotes function of thyroid hormones -> DNA binding, transcriptional effects (target genes to increase metabolic effects)
What are the thyroid function tests?
- Total T4: includes TBG-bound T4 (50-150mmol/L)
- Free T4: only free hormone (10-25pmol/L)
- Total T3
- Free T3
- TSH
- Antibodies (TPO - thyroid peroxidase; TSH-R - may drive proliferation of follicular cells)
What are the thyroid tests of someone with an overactive thyroid? Underactive thyroid?
Overactive: HIGH T4 + T3; LOW TSH
Underactive: LOW T4 + T3; HIGH TSH
Name 3 conditions that cause a thyroid disorder but not as a result of thyroid function?
- Pregnancy/OCP -> increased thyroid-binding globulin (high T4)
- Amiodarone -> hypothyroidism
- Pituitary disease -> pituitary hypothyroidism
What are the 4 causes of thyrotoxicosis (hyperthyroidism)?
- Grave’s Disease (most common!)
- Antibody stimulation of TSH-receptor
- Molecular mimicy
- Autoimmune mechanism, may remit
- Diffuse goitre, increased blood supply = bruits over thyroid
- Affects younger people - Multinodular Goitre
- Multiple thyroid nodules which become independent of TSH regulation
- Won’t remit
- Affects older people - Solitary Toxic Nodule
- Solitary benign adenoma
- Query TSH receptor activating mutation - Drugs
- Interferon (Hep C treatment)
- Amiodarone (Arrhythmia treatment)
What system is most commonly affected by hyperthyroidism side effects?
Cardiovascular system
- High HR, BP
- Altered heart function (i.e. cardiac output)
- Arrhythmias (AF = 3x more likely in > 60y)
What are the symptoms of hyperthyroidism?
- Weight loss with an appetite
- Tachycardia, palpitations, AF
- Heat intolerant, sweating
- Irritable mood
- Frequent bowel movements
- Goitre
- Eye signs: exopthalmos
- Thyroid eye disease: peri-orbital oedema + conjunctivial oedema (chemosis) -> risks = corneal ulceration, optic nerve damage -> blindness
What are the treatments for thyrotoxicosis?
{B-adrenergic blockers = reduction of symptoms (ie. propranolol)}
- Antithyroid drugs
- Carbimazole (1/day)
- Propylthiouracil (2-3/day)
- Titrate dose down, 6mo-2y treatment - Radioactive iodine
- Pretreat with antithyroid drugs to prevent thyroid crisis
- Kills thyroid follicular cells = risk of hypothyroidism - Surgery (sub/near-total thyroidectomy)
- Permanent PTH damage
- Vocal cord paralysis
- Bleeding
- Keloid scarring
- Hypothyroidism inevitable
What are the side effects of antithyroid drug treatment?
- Rash, itch
- Arthralgia
- N/V
- Leukopenia (decreased number of leukocytes)
- Agranulocytosis (no neutrophil production, 1:2000 risk of fatal bacterial infection)
What are the ratios of T4:T3? Which form is more active? Free:Protein-Bound?
Approximately 10x more T4 is released than T3
T3 is 10x more active than T4. T4 deiodinates into T3 in peripheral tissues.
99% of thyroid hormones are protein-bound (small proportion that are unbound = physiologically active)
What is thyroid crisis?
Thyroid storm is a life-threatening health condition that is associated with untreated or undertreated hyperthyroidism. During thyroid storm, an individual’s heart rate, blood pressure, and body temperature can soar to dangerously high levels. Without prompt, aggressive treatment, thyroid storm is often fatal.
What arteries supply the thyroid gland?
Superior/inferior thyroid arteries (branches of the aorta)
How does radioactive iodine work? What are its complications?
Radioactive iodine-131 is taken orally and is then rapidly taken up by the thyroid gland. There the release of radiation destroys the tissue over a period of 6-18 weeks.
Early complications include neck discomfort and possible precipitation of Graves’ opthalmopathy. Longer term there is a progressive incidence of hypothyroidism with most patients requiring treatment with thyroxine after several years.
Which symptoms have the greatest ability to discriminate between euthyroidism and hypothyroidism?
- Hoarse/deep voice
- Myalgia + muscle weakness
- Constipation
- Cold intolerance
What is the most common cause of primary hypothyroidism in adults in the UK?
Chronic autoimmune thyroiditis (Hashimoto’s)
- More common in women, associated with other autoimmune diseases
What is secondary hypothyroidism?
Due to TSH deficiency due to pituitary or hypothalamic disease. The thyroid function tests show low free T4 and low TSH levels
How do you know when a thyroxine dose is sufficient?
- Resolution of symptoms
- TSH levels within reference range
What are the possible side effects of over replacement of thyroxine?
- Atrial fibrillation
2. Osteoporosis
What are the red flag symptoms of a lump in the neck?
- Dysphagia
- Neck pain
- Hoarseness
- History of radiation to neck
- Family history of thyroid cancer
What is the investigation of choice for a thyroid lump?
Ultrasound followed by fine needle aspiration of the lump
What are the main histological types of thyroid carcinoma?
- Papillary carcinoma (70%)
- Follicular carcinoma (20%)
- Anaplastic carcinoma (3%)
- Lymphoma (2%)
- Medullary cell carcinoma (5%)
Papillary and follicular carcinomas are derived from the follicular epithelium and are well differentiated and have a good prognosis. Medullary cell carcinomas arise from the calcitonin-C cells in the thyroid.
How is thyroid cancer treated?
- Surgery (total thyroidectomy or lobectomy)
- Post-operative radioactive iodine treatment
- Thyroid hormone suppression (to suppress TSH so that tumour growth is not stimulated)
The patient currently takes 50mcg of thyroxine. Thyroid function tests show the following:
Free T4: 12pmo/L (10-12)
TSH: 5.9 mU/L (0.35-5)
What dose of thyroxine should the GP prescribe?
Increase dose to 75mcg daily
Martin Kerry is a 75yr old man who presents with lack of energy. He has a history of myocardial infarction and has weekly angina attacks. His thyroid functions show Low T4 and High TSH.
What dose of thyroxine should he be prescribed?
25mcg daily
Elderly patients and those with known ischemic heart disease of severe hypothyroidism should be prescribed thyroxine in a low dose of 25mcg daily and increasing in 25mcg steps every 4 weeks. This is because higher doses of thyroxine may worsen angina or precipitate MI
Susan has noticed a lump in the L side of her neck for the past few weeks. The GP detects a solid lump 2cm in diameter in the L lobe of the thyroid and enlarged L-sided cervical lymph nodes. Susan volunteers that her brother had 1 adrenal gland removed last year due to a tumour. What is the most likely diagnosis?
Medullary cell carcinoma
- Can be an inherited condition
- Associated with pheochromocytoma (adrenal tumour) + hyperparathyroidism
Louise Reed is a 28-year-old lady who delivered a healthy baby boy 10 weeks ago. She had a difficult time after delivery. She suffered a post-partum haemorrhage and required a blood transfusion. Since the delivery, Louise has felt exhausted and was disappointed that she was unable to breast feed as she couldn’t produce any milk. Her thyroid function tests show:
Free T4: 6 pmol/L (10-21)
TSH: 0.2 mU/L (0.35-5.0)
What is the most likely diagnosis?
Secondary hypothyroidism.
This is a typical presentation of secondary hypothyroidism due to pituitary infarction post-partum (Sheehan’s syndrome). The patient is likely to also be deficient in ACTH, gonadotrophins and prolacitin.
Prescribe an appropriate increase in a patient’s dose of levothyroxine from 50mcg daily if his TSH is 6.9mU/L.
Levothyroxine, 75mcg, oral
What is the commonest cause of hypothyroidism?
Hashimoto’s Thyroiditis
- Chronic lymphocytic thyroiditis
- T-cell infiltrates destroy thyroid tissue
- May cause firm goitre in early stages
- Autoantibodies: TPO, Thyroglobulin
- Women > men 10:1, age, 40+
What are the features of hypothyroidism
- Weight gain
- Lethargy
- Cold intolerance
- Cool, dry skin
- Dry brittle hair, nail changes
- Constipation, heavy periods (menorrhagia -> iron deficiency anemia)
- Muscle cramps
What are the tests for hypothyroidism?
Low T4, High TSH
- T3 unhelpful often maintained low/normal
What is subclinical hypothyroidism?
- Early thyroid failure
- Raised TSH, still maintained T3/T4
- May be symptomatic
- Progresses to overt hypothyroidism over years
- TSH >2 = HPT axis disturbances, indicates indication for T4 replacement b/c increased risk of hypothyroidism
What is the treatment for hypothyroidism?
Thyroxine (T4)
- 50-150ug, mostly 100-125ug/day
- once daily
- No side effects
- Monitor dose with TFTs, long 1/2 life of T4
- Issues of interference with absorption if taken alongside iron
What is a goitre?
Enlarged thyroid
- Must assess status of thyroid
- Compression symptoms?
- Diffuse
- Graves, hypothyroidism, colloid goitre (euthyroid), iodine deficiency (most common): drugs (i.e. lithium) - Multinodular
* Differentiate by palpation and Ultrasound
What are thyroid nodules (solitary lump)?
Increase with age, normal
30-60% of normal thyroids have nodules
Part of multi nodular disease
What is the diagnostic approach of a solitary lump?
Thy1-Thy5 (benign - malignant)
- Majority have Thy2 (70% colloid nodules)
Where do T3 and T4 exhibit negative feedback in the HPT axis?
On TSH and TRH in the thyroid and hypothalamus respectively
What are the values (high/low/normal) of free T4, T3, and TSH respectively for the following conditions:
- Primary hyperthyroidism
- Secondary hyperthyroidism
- Primary hypothyroidism
- Secondary hypothyroidism
- HIGH T4, HIGH T3, LOW TSH
- HIGH T4, HIGH T3, HIGH TSH
- LOW T4, LOW T3, HIGH TSH
- LOW T4, LOW T3, LOW/NORMAL TSH
What are causes of secondary hyperthyroidism?
- Pituitary adenoma (TSH-oma)
- Gestational thyrotoxicosis (human chorionic gonadotropin)
- HCG producing tumour
What is the cause of secondary hypothyroidism?
Not enough TSH (due to hypopituitarism) - very rare
What is the difference between thyrotoxicosis and hyperthyroidism? Give an example using T3/T4 values to compare Grave’s Disease and thyroiditis.
Thyrotoxicosis = increased circulation of thyroid hormones in the blood (not necessarily hyperthyroidism -> problem with the thyroid itself)
Grave’s Disease: Higher T3 than T4
Thyroiditis: Higher T4 than T3 + Increased TPO and no TSH antibodies present (showing not an autoimmune condition) (i.e. post-partum)
What signs of hyperthyroidism are specific to Grave’s Disease?
- Eye disease (Thyroid eye disease): exophthalmos, ophthalmoplegia
- Pretibial myxoedema: oedematous swellings above lateral malleoli
- Thyroid acropachy: extreme manifestation, with clubbing, painful finger + toe swelling, and periosteal reaction in limb bones
How would you treat postpartum thyroiditis?
Usually self-limiting condition, but can treat symptoms with beta-blocker (propranolol)
What is the epidemiology of postpartum thyroiditis?
It’s a type of Hashimoto’s thyroiditis although can be hyperthyroidism or hypothyroidism
Common condition (7% of population affected)
Look for eye signs, fT3 + TRAB (TSH receptor antibodies)
- TRAB is the most useful distinguishing factor from Grave’s
Requires annual TFTs to be checked
What values would you see on TFTs in subclinical hypothyroidism?
Slightly increased TSH + normal T3 + T4
How would you treat a patient with high cholesterol as a result of their hypothyroidism (remember there’s a link between thyroid dysfunction - hypothyroidism - and high cholesterol)
Thyroxine 75mcg daily, starting dose
- If there’s underlying cardiac disease decrease starting does (i.e. 50mcg)
- Repeat TFTs 2-3mo later
** Remember the lower the T4 + T3 the greater the risk of high cholesterol!**
What are two possible problems that can occur during pregnancy to the pituitary gland?
- Pituitary Apoplexy: bleeding into/impaired blood supply to the pituitary.
Symptoms:
- Sudden onset headache
- Double vision caused by compression of optic nerve (bitemporal hemianopia) - Sheehan’s Syndrome: also known as postpartum pituitary gland necrosis, is hypopituitarism (decreased functioning of the pituitary gland), caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth.
What is panhypopituitarism?
Occurs in adulthood once > 75% of the anterior pituitary cells are destroyed.
Causes:
- Tumours compressing on pituitary until anterior cells are destroyed
- Thrombosis of pituitary blood vessels (i.e. Sheehan’s Syndrome)
General Effects:
- Hypothyroidism
- Depressed production of glucocorticoids by adrenals (Addison’s)
- Suppressed secretion of gonadotropin hormone (lost libido)
Treatment:
- Adrenocortical + anti-thyroid hormones
What is an adrenal crisis and its symptoms?
Also termed acute adrenal insufficiency is an acute life-threatening condition. It is considered one of the endocrine emergency precipitated by an internal or external process in the setting of known or unknown lack of production of the adrenal hormone cortisol, the major glucocorticoid.
Symptoms of an Addisonian Crisis (adrenal crisis):
- extreme tiredness and weakness
- confusion, psychosis, and slurred speech.
- dizziness and feeling faint
- nausea, vomiting, loss of appetite, and stomach pain.
- fever, chills, and sweating.
- sudden lower back or leg pain.
- dangerously low blood pressure.
- fast heart rate.
What is the risk of over-replacement of thyroid hormones? When should thyroid treatment be given normally?
- Osteoporosis
- AF
Should be given 30min before breakfast
How long does it take for thyroid medications to have an effect on T3, T4, TSH?
TSH takes a few weeks for the negative feedback to work.
T3 and T4 will immediately go back to normal levels
