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.
