S3C9 (2.0) Flashcards
What is the thyroid?
A butterfly-shaped, unpaired endocrine gland composed of two lobes
Where is the thyroid?
Located anteriorly in lower part of neck
C5-T1
Surrounded by pretracheal fascia
What are the anterior relations to the thyroid?
Strap muscles (sternohyoid, sternothyroid, thyrohyoid, and omohyoid muscles)
What are the posterior medial relations to the thyroid?
Trachea
Oesophagus
Recurrent laryngeal nerve
External branch of superior laryngeal nerve
What are the posterior lateral relations to the thyroid?
Parathyroid glands
Cricoid cartilage
Lower thyroid cartilage
Carotid sheath - internal jugular vein, vagus nerve, and common carotid artery
What is the function of the thyroid?
Produce thyroid hormones that are essential for regulation metabolism and growth
What connects the two lobes of the thyroid?
Isthmus
What encapsulates the thyroid?
Pretracheal fascia - false/surgical capsule
Internal capsule - inner connective tissue covering that cannot be separated from the gland (true capsule)
What does the internal capsule around the thyroid form?
Septae, dividing the gland into lobes and lobules
What supplies the superior and anterior part of the thyroid?
Superior thyroid artery (from external carotid)
What supplies the posterior and inferior part of the thyroid?
Inferior thyroid artery (the thyrocervical trunk - branch of subclavian artery)
What does the thyroid ima artery supply?
Anterior surface of isthmus
Present in 10% of people
from the brachiocephalic trunk of the arch of aorta
What is the venous drainage of the thyroid?
Superior and Middle thyroid vein - drains into IJV
Inferior thyroid vein - drain into r/l brachiocephalic veins
What nodes are involved in lymphatic drainage of the thyroid?
Paratracheal nodes
Deep cervical nodes
What nerve provides the parasympathetic innervation for the thyroid?
Vagus
What provides the sympathetic innervation for the thyroid?
Superior, middle, and inferior cervical ganglia of the sympathetic trunk
What are thyroid follicles?
Small functional units
Spherical, vesicular components of the thyroid gland lined with epithelium
Follicular lumen filled with colloid
What are the two types of cells forming epithelium of thyroid follicles?
Thyroid epithelial cells
C cells
What fills the interfollicular spaces in the thyroid?
Reticular connective tissue Fenestrated capillaries - facilitate the release of hormones into the blood Lymphatic vessels Adipocytes Sympathetic nerves
How are thyroid epithelial cell arranged?
Basophilic cuboidal epithelium
Arranged in spherical follicles surrounding colloid
What receptors are found on the surface of thyroid epithelial cells?
TSH receptors
What is the function of thyroid epithelial cells?
Take up amino acids and iodine on basolateral side from blood
Synthesise, secrete and store thyroid peroxidase and thyroglobulin
What is thyroglobulin?
A protein made in the thyroid gland that is a precursor to thyroid hormone.
What is thyroid peroxidase?
An enzyme in the thyroid gland which catalyses the addition of iodine onto thyroglobulin to make thyroxine (T4) or triiodothyronine (T3)
How are C Cells arranged?
Large pale staining cells between thyrocytes
Found along the basement membrane of thyroid epithelium, which surrounds follicles and has no direct contact with lumen
How are C Cells activated?
Calcium-sensing receptors (CaSR) on surface
High extracellular calcium activates G-protein-coupled second-messenger (IP3 and DAG)
Increase of intracellular Ca2+ levels which increases calcitonin release
What is the function of C Cells?
Hormone production and storage in granules
Procalcitonin → proteolytic cleavage of N- and C-terminal peptide → calcitonin
Also secretes several neuroendocrine peptides in smaller quantities such as serotonin, somatostatin, dopamine, TRH, and motilin
What is the function of calcitonin?
Lowers calcium in serum
What is the function of calcitonin in bones?
Increase osteoclast activity
What is the function of calcitonin in kidneys?
Increases excretion of calcium and phosphate
What is the function of calcitonin in the intestine?
Lowers calcium absorption
What is the process of thyroid hormone synthesis?
- Thyroglobulin, an iodine-free hormone precursor, is stored in the follicular lumen.
- Iodide is actively taken up by thyrocytes and transported into the follicular lumen.
- Here, thyroid peroxidase catalyses the iodination of tyrosine residues of thyroglobulin, creating precursors monoiodotyrosine (MIT) and diiodotyrosine (DIT) and eventually the thyroid hormones.
How is T3/T4 released from the follicular lumen?
The iodinated thyroglobulin must be taken up again by thyrocytes, where it is broken down by lysosomes, thus releasing attached T4 and T3.
T4 and T3 are then transported out of the thyrocyte into the blood
What are the transport proteins involved in transporting thyroid hormone?
Primarily thyroxine-binding globulin (TBG)
Transthyretin: transports thyroxine and retinol
Albumin
How is thyroid hormone degraded?
Degraded in liver
sulfation/glucuronidation (biotransformation) → excretion via bile
What is the effect of thyroid hormone on the heart?
Increased cardiac beta-receptors Increased heart rate Increase stroke volume Increase cardiac output Increased contractility
What is the effect of thyroid hormone on the lungs?
Stimulation of the respiratory centre
Increase oxygenation due to increased lung perfusion
What is the effect of thyroid hormone on skeletal muscle?
Increased development of type 2 muscle fibres
What is the effect of thyroid hormone on metabolism?
Increased metabolic rate due to increased expression of Na+/K+ ATPase in many tissues
What is the effect of thyroid hormone on growth during childhood?
stimulation of bone growth
induction of chrondrocytes, osteoblasts and osteoclasts
promotion of synthesis and secretion of growth hormone
What is the parathyroid gland?
Four, oval-shaped endocrine glands embedded in the posterior surface of the thyroid gland
Where are the two superior parathyroid glands located?
Near the superior pole of the thyroid gland at the junction of cricoid and thyroid cartilages
Where are the two inferior parathyroid glands located?
Located in the area between the inferior poles of the thyroid lobes and the superior mediastinum
What is the function of the parathyroid glands?
Secretion of parathyroid hormone (PTH) in response to low calcium serum levels
What is the vasculature of the parathyroid gland?
Arterial supply: inferior thyroid arteries
Venous drainage: thyroid plexus of veins
Lymphatic drainage: deep cervical nodes, paratracheal nodes
What innervated the parathyroid gland?
Thyroid branches of the cervical ganglia
What different cells are found in the parathyroid gland?
Adipocytes (∼ 50%) Parathyroid cells (parathyroid chief cells) Oxyphil cells: red/pink cytoplasm; function not clear
What are parathyroid cells?
Polygonal, hormone-secreting cells with round nucleus
Produce and secrete PTH
Have calcium-sensing receptors (CaSR), which detect changes in calcium concentration and modulate PTH secretion
What are the adrenal glands?
Two endocrine glands that produce steroid hormones and adrenaline
What is the approximate size of the adrenal gland?
Height and thickness ~5cm and width 1-2cm
Where are the adrenal glands located?
Primary retroperitoneal organs
Each gland is located superior to the upper pole
Enclosed by the renal fascia and adipose capsule of the kidney
Whats the function of the adrenal gland?
Adrenal cortex: outer layer produces steroid hormones
Adrenal medulla: inner part produces catecholamines
What is the arterial blood supply to the adrenal glands?
Superior suprarenal artery (from the inferior phrenic artery)
Medial suprarenal artery (from the abdominal aorta)
Inferior suprarenal artery (from the renal artery)
What is the venous drainage from the adrenal glands?
Right suprarenal vein into the inferior cava vein
Left suprarenal vein into the left renal vein
What is the lymph drainage from the adrenal glands?
Left - aortic lymph nodes
Right - caval lymph nodes
What is the innervation of the adrenal gland?
Sympathetic - major and minor splanchnic nerves from coeliac ganglion
Parasympathetic - vagal nerve
What are the layers of the adrenal cortex?
Zona glomerulosa
Zona fasciculata
Zona reticularis
What is the structure of the zona glomerulosa?
Cells arranged in oval clusters surrounded by connective tissue from the fibrous capsule
What is the function of the zona glomerulosa?
Mineralocorticoid synthesis - regulates of renal sodium and water reabsorption and potassium excretion
What is the structure of the zona fasciculata?
Cells arranged in straight columns that are separated by small fibrous septa
Steroid synthesizing cells contain many lipid droplets that contain the cholesteryl ester for steroid production
What is the function of the zona fasciculata?
Glucocorticoid synthesis - metabolism: mobilise energy reserves
What is the structure of the zona reticularis?
Small cells arranged in an irregular netlike formation surrounded by connective tissue and capillaries
What is the function of the zona reticularis?
Androgen synthesis -precursor for oestrogen and testosterone
What is the structure of the adrenal medulla?
Large chromaffin cells with many secretory granules (catecholamine storage)
What is the function of the adrenal medulla?
Synthesis of catecholamines
What is the hypothalamic-pituitary gland-adrenal cortex feedback mechanism?
corticotropin-releasing hormone (CRH) → increased secretion of adrenocorticotropic hormone (ACTH) in the pituitary gland → increased secretion of glucocorticoids in the adrenal cortex
What does the presence of TSH receptor autoantibodies and/or Thyroid peroxidase antibodies suggest?
An autoimmune thyroid disorder such as Graves or Hashimoto’s
What does the presence of thyroglobulin antibody indicate?
Thyroid cancer
What is BMI?
The body mass index (BMI) is a measure that uses your height and weight to work out if your weight is healthy.
What are the BMI ranges?
below 18.5 – you’re in the underweight range
between 18.5 and 24.9 – you’re in the healthy weight range
between 25 and 29.9 – you’re in the overweight range
between 30 and 39.9 – you’re in the obese range
What is the BMI formula?
The formula is BMI = kg/m2 where kg is a person’s weight in kilograms and m2 is their height in metres squared.
Explain the fight/flight response pathway.
Hypothalamus activates the sympathetic nervous system. This activates smooth muscles and the adrenal medulla to release noradrenaline and adrenaline into the bloodstream.
At the same time, the hypothalamus stimulates the anterior pituitary gland to release corticosteriod releasing factor.
The pituitary gland the secretes ACTH, which arrives at the adrenal cortex to release ~30 hormones
What happens if there is a prolonged threat?
in regards to fight/flight
If threat continues, the hypothalamic-pituitary-adrenal axis activates.
Keeps the sympathetic nervous system active
Releases cortisol
What percentage of people have a long term anxiety problem in England?
17.6%
What is the recovery rate for someone with anxiety in England?
51%
Describe the Hypothalamus-Anterior pituitary-thyroid axis
The hypothalamus secretes TRH.
This stimulates the A Pituitary to secrete TSH
This activates the thyroid to produce T4 and T3.
T3 inhibits both the anterior pituitary and the hypothalamus secretions
What is T4 broken down into?
Reverse T3
What is T3 broken down into?
T2
How much of each thyroid hormone is secreted?
80% T4
20% T3
How much of T4 is metabolised into T3?
40%
When treating someone, why do you give them T4 supplements instead of T3?
T4 lasts longer in body
T3 half-life is 1-3 days
T4 half-life is 5-7 days
What is the action of T3?
T3 binds to the Thyroid receptor attached to the retinoid X receptor
This affects gene expression
Meaning slow acting
Describe the epidemiology of hyperthyroidism
1% of the general population Sex women:men 7:1 Ages: Graves disease: 20–30 years Toxic adenoma: 30–50 years Incidence of toxic multinodular goitre: peak incidence > 80 years of age
What are the different ways hyperthyroidism can occur?
Hyperfunctioning thyroid gland - overproduction of thyroid hormones
Destruction of the thyroid gland - release of preformed thyroid hormones secondary to inflammation/destruction
Exogenous hyperthyroidism - excessive intake of thyroid hormones
Exctopic hormone production
What are examples of hyperfunctioning hyperthyroidism?
Graves disease (60%-80% of cases)
Toxic multinodular goitre (15-20% of cases)
Toxic adenoma (3-5% of cases)
TSH-producing pituitary adenoma
β-hCG mediated hyperthyroidism - pregnancy 2.5%
Hashitoxicosis
What are the signs of fetal hyperthyroidism?
> 160bpm fetal
Goitre
Advanced neonatal bone age
craniosynotosis
What can happen when pregnant with Graves?
Spontaneous abortion Premature labour Small birth weight Congestive cardiac failure Pre-eclampsia 1% generate fetal hyperthyroidism - placental crossing of TSHR stimulation Abs
What are the effects of hyperthyroidism?
Generalised hypermetabolic state - increased substrate consumption
Hyperstimulation of the sympathetic nervous system
Cardiac effects - caused by a direct effect of thyroid hormones on the cardiac myocytes and the hyperadrenergic state.
What are the Basic clinical features of hyperthyroidism?
Heat intolerance, excessive sweating Weight loss despite increased appetite Hyperdefecation Weakness, fatigue Hyperreflexia Eye issues Diffuse, smooth, nontender goiter
What are the eye-related symptoms of hyperthyroidism?
Lid-lag - Sclera visible above the cornea when looking down
Lid retraction - Sclera visible above the cornea when looking straight ahead
Graves opthlmopathy
What causes lid lag?
An adrenergic overactivity resulting in a spasm in the smooth muscle portion of the levator palpebrae superioris
What are the cardiovascular symptoms of hyperthyroidism?
Tachycardia:
Palpitations, irregular pulse (due to atrial fibrillation/ectopic beats)
Hypertension with a widened pulse pressure
Cardiac failure
What are the musculoskeletal symptoms of hyperthyroidism?
Fine tremor of the outstretched fingers
Myopathy with muscle weakness, particularly in patients > 40 years of age
Osteoporosis , fractures (in the elderly)
What are the Endocrinological symptoms of hyperthyroidism?
Women: Oligo/amenorrhoea and anovulatory infertility
Men: Gynecomastia, decreased libido, erectile dysfunction
What are the Neuropsychiatric symptoms of hyperthyroidism?
Anxiety Agitation Depression Insomnia Emotional instability
Why use a thyroid ultrasonography?
Thyroid ultrasonography is particularly useful in evaluating hyperthyroidism in pregnant women since scintigraphy is contraindicated in this group of patients.
What is a thyroid scintigraphy?
A nuclear medicine imaging technique, which demonstrates the structure and function of thyroid tissue based on its selective uptake of radioactive iodine (RAI)
When would you use a thyroid scintigraphy?
Patients in whom the aetiology is uncertain or if physical examination suggest nodular thyroid disease
Identification of ectopic thyroid tissue
Evaluation of thyroglossal cyst
When wouldn’t you use a thyroid scintigraphy?
Pregnant or breast-feeding
What can be given to treat the symptoms of hyperthyroidism?
Beta-blockers offer immediate control of symptoms - Improve tachycardia, hypertension, tremor and neuropsychiatric symptoms
Propranolol decreases peripheral conversion of T4 to T3 by inhibiting the 5’-monodeiodinase enzyme
What different definitive therapies can be used to treat hyperthyroidism?
Anti-thyroid drugs
Radioactive iodine ablation
Surgery
What are the indications of anti-thyroid drugs?
Patients with high likelihood of remission
Active Graves ophthalmopathy
Children ≤ 5 years
Pregnancy
Thyroid storm
Patients who need rapid disease control
Patients with an inability to follow radiation safety regulations
What is the permanent remission rate after 1-2 years of treatment?
20-75%
What is the drug of choice for hyperthyroidism when the patient is pregnant or in a thyroid storm?
Propylthiouracil
What is radioactive iodine ablation?
The destruction of thyroid tissue using radioactive iodine (iodine 131) through a sodium/iodine symporter
What are the indications for using RAIA?
High surgical risk; limited life-expectancy
Liver disease
Major adverse reaction to ATDs
Previous operations or radiation of the neck
Patients with congestive heart failure, right heart failure, pulmonary hypertension, or periodic hypokalemic paralysis
When shouldn’t you treat hyperthyroidism with RAIA?
Pregnant/breastfeeding
Children <5
Thyroid malignancy
Moderate to severe Grave ophthalmopathy
How does RAIA work?
Single oral dose of 131 Iodine
Isotope uptake by thyroid gland
Emission of β-radiation that slowly destroys the thyroid tissue
What are the indications for thyroid surgery?
Large goiters (≥ 80 g) or obstructive symptoms
Confirmed or suspected thyroid malignancy
Moderate to severe active Graves ophthalmopathy
Women planning to become pregnant in the next < 6 months
What are the contraindications for surgery?
Severe comorbidities that influence surgical risk
1st and 3rd trimester of pregnancy
What is a thyroid storm?
Thyrotoxic crisis
An acute exacerbation of hyperthyroidism, resulting in a life threatening hypermetabolic state
What is the aetiology of a thyroid storm?
A sudden surge in thyroid hormones
Stress-related catecholamine surge - worsened the pre-existing hyperadrenergic state of hyperthyroidism
What are the clinical features of a thyroid storm?
Hyperpyrexia w/ profuse sweating Tachycardia Hypertension AF Congestive cardiac failure Severe nausea Vomiting Diarrhoea Possibly jaundice Severe agitation and anxiety Delirium and psychoses Seizures Coma Low/ undetectable TSH Elevated free T3/T4
What are the immediate treatments available for thyroid storm?
IV dextrose solutions are preferred to meet the high metabolic demand
Treatment of hyperthermia: ice packs, cooling blankets, and antipyretics (e.g., acetaminophen)
What is the epidemiology of Graves disease?
~30 cases per 100,000 people per year
8:1 w:f
20-40 years
What are the genetic predispositions linked with Graves?
50% of patients have family history of autoimmune disorders
Associated with HLA-DR3 and HLA-B8 alleles
What cells mediate graves?
B and T lymphocyte mediated
What infectious agents can trigger Graves?
Yersinia enterocolitica and Borrelia burgdorferi - shown to trigger antigen mimicry for homologies between their protein constituents and thyroid autoantigens
How does pregnancy increase the risk of Graves?
Thyroid overstimulation by high levels of hCG and TRAb during the first trimester
How does the second trimester of pregnancy decrease the risk of Graves?
Progesterone-induced immunosuppression.
Why does the risk of Graves increase postpartum?
A drop in progesterone level which leads to the rebound of the immune system that can trigger autoimmunity
What is the pathophysiology of Graves?
B and T cell-mediated autoimmunity
Production of stimulating immunoglobulin G (IgG) against TSH-receptor (TRAb; type II hypersensitivity reaction)
↑ thyroid function and growth
How does Thyroid-associated ophthalmopathy occur in Graves?
activated B and T cells infiltrate retro-orbital space targeting orbital fibroblasts
Cytokine release (e.g. TNF-α, IFN-γ) → local inflammatory response
Fibroblast proliferation and differentiation to adipocytes
Production of hyaluronic acid and GAGs and increased amount of adipocytes
Increase in the volume of intraorbital fat and muscle tissues
How does pretibial myxoedema occur?
dermal fibroblast stimulation and deposition of glycosaminoglycans in connective tissue
What are the histological features of an overactive thyroid?
Diffuse hyperplasia of thyroid follicles
Hyperplastic and hypertrophic follicular cells
Colloid reabsorption with peripheral scalloping
Irregular stromal lymphocytic infiltration
How many newborns have congenital hypothyroidism a year?
1/2000-1/4000
What is the cause of primary hypothyroidism?
Insufficient thyroid hormone production
What is the cause of secondary hypothyroidism?
Pituitary disorders - thyroid stimulating deficiency
What is the cause of secondary hypothyroidism?
Hypothalamic disorders -
Thyrotropin-releasing hormone deficiency
What are the effects of hypothyroidism?
Generalised decrease of the basal metabolic rate
myxoedema - increased deposition of glycosaminoglycans
Hyperprolactinemia - stimulated by TRH
What are the symptoms of a decreased metabolic rate?
Fatigue, bradykinesia Cold intolerance Cold, dry skin, and hair loss Weight gain (despite poor appetite) Constipation Myopathy , myalgia, stiffness, cramps, delayed tendon reflex relaxation, entrapment syndromes (e.g., carpal tunnel syndrome)
What are the symptoms linked to myxoedema?
Doughy skin texture, puffy appearance Myxedematous heart disease (dilated cardiomyopathy, bradycardia, dyspnoea) Myxoedema coma Hoarse voice, clumsy speech Pretibial and periorbital oedema
What are the symptoms of hyperprolactinemia?
Abnormal menstrual cycle (esp. secondary amenorrhea or menorrhagia)
Galactorrhoea
Decreased libido, erectile dysfunction, delayed ejaculation and infertility in men
