Block 6: thyroid, osteomalacia Flashcards
1
Q
Markers of bone activity
A
- Bone resorption (Osteoclast activity): N-terminal telopeptide of type I collagen (NTX), C-terminal telopeptide of type I collagen (CTX), Hydroxyproline
- Bone formation (Osteoblast activity); Alkaline phosphatase (bone specific), Osteocalcin, N-terminal propeptide of type I procollagen (P1NP
2
Q
Bone mineral density: BMD
A
- Measured by dual X-ray absorptiometry (DXA) at hip and spine (g/cm2): done for a particular area
- Z-score: BMD compared to age matched population
- T-score: BMD compared to race and sex matched peak adult BMD- young adult
- Both expressed as standard deviations from population mean
3
Q
Osteoporosis
A
- Common problem in elderly population
- Hip fracture commonly leads to death
- Defined in several ways: Clinically- presence of low-impact fracture: Hip, Lumbar spine, Colles. Radiographically- presence of low bone mineral density
- Reduced bone mass
- Normal biochemistry
4
Q
Fragility fracture and deformity
A
NOF, vertebral collapse, wrist, vertebral. Vertebral fractures cause loss of height and thoracic kyphosis. Fragility fracture is from standing height or less
5
Q
T score criteria
A
- Fragility fracture defines ‘Established osteoporosis’: not reliant on bone density
- T score of -2.5 or less is WHO definition of osteoporosis
- T score of -1 to -2.5 defines osteopenia
6
Q
Factors affecting bone mass and loss
A
- Increased: gets higher between 0 and 30, exercise, increased calcium intake
- Worse: Menopause, drugs, disease, iron deficiency, immobility
7
Q
Risk factors for osteoporosis
A
- Low weight (<55kg), tall height (>5’7”)
- Smoking & Alcohol use
- Medication use (steroids)
- Premature menopause, hypogonadism
- Low calcium intake
- Family History
- Ethnic background: South asian
8
Q
Secondary osteoporosis
A
- Malabsorption, Hepatic or Renal disease
- Endocrine problem: Hypogonadism, thyrotoxicosis, hyperparathyroidism, Cushings
- Drugs: Steroids, anticonvulsants, heparin
- Others: Rheumatoid arthritis, Osteogenesis imperfecta, Systemic mastocytosis, Immobilization, weightlessness
9
Q
Osteopenia treatment- risk stratifying to prevent osteoporosis
A
- Increase Calcium intake (>1200 mg/day): diet (dairy or green cabbages) or medication
- Increase Vitamin D intake (>800 U or 20mcg /day): Cholecalciferol
- “Life-style” - Weight-bearing exercise
- These measures can also be used in osteoporosis
10
Q
Treatment for osteoporosis
A
- Bisphosphonates (Alendronate: oral weekly or Zolendronic acid: IV annually)
- Denosumab (anti-RANKL mAb): SC every two years
- Hormone replacement therapy: Menopause, hypogonadism, use before vitamin D and calcium replacement
- Selective estrogen receptor modifiers (SERM): Roloxifene, used in milder osteoporosis
- PTH injections: help bone to growth. Teriperatide daily injection
- Romosozumab- anti-sclerostin mAb: if failed to improve bone density or fracture after Bisphosphonate course. Help bone to grow
11
Q
Investigations for osteoporosis and how to take Bisphosphonates
A
- FRAX score: to determine whether to treat, shows risk of any major fracture
- BMD
Taking Bisphosphonates: Need to be standing up (can cause oesophagitis)
12
Q
Sources of vitamin D
A
- Sunlight (UVB) on exposed skin. 1,25- Dihydroxy vit.D3 is the active form. Sun cream stops vitamin D production.
- Oily fish: Salmon, trout, mackerel, tuna, anchovy, sardine, pilchard etc.
- Small amount in meat, egg yolk
- Mushrooms (grown outdoors)
- A persons average levels of vitamin D change with the season
13
Q
Vitamin D levels: osteomalacia
A
- > 75: optimal, healthy
- 50-75: adequate vitamin D, Healthy, offer lifestyle advice
- 25-50: insufficient vitamin D, associated with disease risk, supplement with vit D
- <25: deficient, rickets and osteomalacia, treat with high dose vit D
14
Q
pathophysiology of osteomalacia
A
- Mineralisation defect in the bone: lack of vitamin D impairs calcium absorption. Reduced mineralisation of osteoid. More unmineralized bone so they bend. Also low phosphate
- Rickets: childhood disease where you can see bends in bone because they are incompletely mineralised. In osteomalacia you don’t see the bent bones as they are already grown
15
Q
Rickets/osteomalacia
A
- Low serum 25-OH vit D
- Elevated PTH
- Elevated alkaline phosphatase
- Hypocalcaemia, hypophosphataemia
- Due to: Lack of sunlight +/- dietary vitamin D, Drugs, Dietary lack of calcium/ phosphate deficiency, Renal or Hepatic disease (lack of activation of vitamin D)
16
Q
Drug induced osteomalacia
A
- Anticonvulsants (induce hepatic D metabolism- more burnt off): should prophylactically receive vitamin D supplements
- Colestyramine/colsevalam (malabsorption)
- Bariatric surgery
- Fat malabsorption (pancreatic insufficiency)
17
Q
Features of osteomalacia
A
- Symptoms: Weakness, myalgia, bone pain, tetany, paraesthesia, dental abnormalities, fractures
- Skeletal: bowing deformities, spinal deformities (kyphosis or scoliosis)
- Rickets (osteomalacia in children): Bowing of legs, knock knees, craniotabes (can indent skull).
18
Q
X-ray appearance of osteomalacia
A
- Cupped epiphyses,
- Loosers zones: bone under mineralisation- pseudo fractures, present as radiolucent band
- Rachitic rosary (enlarged costochondral junctions on ribs)
19
Q
Treatment for osteomalacia
A
- Colecalciferol: 20,000 units oral twice weekly for 12 weeks. Maintainance of 800-1000 U/d forever
- Ergocalciferol: Same doses, Suitable for vegetarians
- Suitable sun exposure: if European descent 20-30 minutes of sunlight on arms and face at midday
20
Q
Osteomalacia investigations and results
A
- Serum 25-hydroxyvitamin D is the laboratory test for vitamin D
- Less than 25 nmol/L –vitamin D deficiency
- 25 to 50 nmol/L –vitamin D insufficiency
- Low serum calcium
- Low serum phosphate
- High serum alkaline phosphatase
- High parathyroid hormone(secondary hyperparathyroidism)
- X-raysmay show osteopenia (more radiolucent bones)
- DEXAscan shows lowbone mineral density
21
Q
Symptoms of pituitary tumours
A
- Can get hormone deficiency or excess
- Acromegaly(excessive growth hormone)
- Hyperprolactinaemia(excessive prolactin)
- Cushing’s disease(excessive ACTH and cortisol)
- Thyrotoxicosis(excessive TSH and thyroid hormone)
- Bitemporal hemianopia: press on the optic chiasm
22
Q
Pituitary tumours can be managed with
A
- Trans-sphenoidal surgery(through the nose and sphenoid bone)
- Radiotherapy
- Bromocriptine to block excess prolactin
- Somatostatin analogues(e.g., octreotide) to blockexcessgrowth hormone
- Hormone treatment for symptoms
23
Q
Pituitary adenoma
A
benign tumours of the pituitary gland. They are either secretory (producing a hormone in excess) or non-secretory. They may be divided into microadenomas (smaller than 1cm) or macroadenoma (larger than 1cm). Investigation requires a pituitary blood profile and MRI.
24
Q
Toxic thyroid adenoma
A
Benign nodular thyroid disease. Causes Hyperthyroidism. 5% of total cases. Definitive treatment with radioactive iodine or surgery. Due to monoclonal proliferation of follicular cells and rarely papillary cells. Symptoms same as hyperthyroidism
Risk factors: Iodine deficiency
25
Q
Toxic thyroid adenoma: on examination
A
- Palpable solitary large nodule. Toxic adenomas are usually >3cm before causing clinical symptoms so often clearly palpable.
- Tracheal deviation may be present if the nodule is large
- Tachycardia
- Lid lag
- Absence of exophthalmos, extraocular muscle involvement (occurs in 25-30% ofGraves’ diseasebut not in thyroid adenoma)
26
Q
Imaging for toxic thyroid adenoma
A
- Thyroid ultrasound: First line imaging of any thyroid nodule, to characterise and confirm adenoma-like (cystic, hypoechoic) and not suspicious of malignancy.
- Radioisotope scanning, using 99mtechnetium or 131iodine: diagnostic for toxic adenoma. If positive radioisotype scan and benign appearance on US no need for other tests
27
Q
Management of toxic thyroid adenoma
A
- Remission with medication is rare need definitive treatment of radioactive iodine therapy or surgery
- Radioactive iodine therapy: contraindicated in pregnancy or lactating women, caution in children. Most only need one dose, some need two. Reduces goitre size
28
Q
Toxic thyroid adenoma- surgery
A
- Surgery: subtotal thyroidectomy is curative in 90% and provides symptom relief from mass effect. Side effects: recurrent laryngeal nerve damage, transient hypocalcaemia
- Indications for surgery include patient preference for, contraindication to radioactive iodine therapy, symptoms of neck compression, or presence of a large nodule with substernal or retrosternal extension.
29
Q
Grave’s disease
A
- Autoimmune-mediated hyperthyroidism, testing positive for TSH-receptor and/or anti-thyroid peroxidase antibodies
- Diffuse goitre rather than a solitary nodule
- Other differentiating signs from adenoma are the presence of exophthalmos, eyelid retraction and extraocular muscle involvement
30
Q
Toxic multinodular goitre
A
- Benign nodular thyroid disease, as adenoma, but with large irregular goitre owing to multiple nodules with different levels of activity
- Second most common cause
- Patients are often older than 40-years-old in contrast to the adenoma population
- Radioisotope scan shows both hot and cold areas of uptake, rather than solitary autonomous hot area.
31
Q
Thyroiditis
A
- An autoimmune-mediated inflammation of the thyroid gland that is usually transient and self-resolving
- Small palpable goitre may be present, with raised ESR
- Anterior neck pain and tenderness
- A key risk factor is for women in the postnatal period
- A radioisotope scan shows little or no uptake
32
Q
Thyroid cancer
A
- Likely associated cervical lymphadenopathy
- Ultrasound scan likely to show suspicious features: irregular hyperechoic mass. Subsequent fine needle aspiration histological diagnosis
- Extra-thyroid uptake on radioisotope scan reveals any metastases
33
Q
Toxic multinodular goitre risk factors
A
Iodine deficiency, head and neck irradiation, >40
34
Q
Symptoms of toxic multinodular goitre
A
- Classic hyperthyroid symptoms
- Older patients: mood changes, weight loss, A-fib
- Warm skin, stare and/or tremor
- Lid lag
- Occasionally dysphagia, hoarseness, cough or choking sensation due to neck compression
35
Q
Investigations for toxic multinodular goitre
A
- Without Graves disease stigmata and TSH receptor antibodies: thyroid scan and uptake are indicated
- Radioisotope scan: multiple hot and cold areas
- Uptake less than Graves and often within normal range
- ECG may be necessary for suspected dysrhythmia.
- CT non-contrast Neck may be indicated for pre-operative evaluation.
36
Q
Toxic multinodular goitre management
A
- Surgery: if the swelling obstructs breathing or swallowing can remove excess tissue. Can get hypocalcaemia due to hypoparathyroidism
- Radioactive iodine: first line
- Carbimazole and supportive care while awaiting specialist assessment
- Beta blockers for symptoms
37
Q
Causes of Hypothyroidism
A
- Autoimmune (Hashimoto)
- Subacute thyroiditis usually viral infection
- Iodine deficiency
- Drugs (amiodarone)
- Irradiation
- Thyroid surgery
- Congenital
- Secondary hypothyroid - Pituitary Disease
38
Q
Thyroid antibodies
A
TRAB (thyroid receptor antibody): confirms Grave’s
TPO (thyroid peroxidase antibodies): diagnosis Hashimotos
39
Q
Clinical features of hypothyroidism
A
- Fatigue
- Weight gain
- Constipation
- Dry skin
- Hair loss
- Cold Intolerance
- Hoarseness
- Sinus Bradycardia
- Goitre
- Delayed relaxation of Deep Tendon Reflexes
40
Q
Hypothyroidism bloods
A
- Primary Hypothyroid (disorder in thyroid): Low Free T3 and FreeT4, High TSH
- Secondary hypothyroid (disorder above thyroid i.e. pituitary): Low Free T3 and Free T4, Low TSH
41
Q
Treatment of Hypothyroidism
A
Daily levo thyroxine - Before breakfast on empty stomach, and follow up with regular thyroid function tests
42
Q
Causes of Hyperthyroidism
A
- Graves Disease
- Toxic Multi Nodular Goitre
- Toxic Nodule
- Drugs (Amiodarone)
43
Q
Grave’s disease
A
- Most common cause of hyperthyroidism
- Auto Immune
- Family History
- Thyroid Associated Eye Disease
- Thyroid Receptor antibody
44
Q
Hyperthyroidism: symptoms and signs
A
- Hyperactivity, irritability
- Heat intolerance
- Weight loss (normal to increased appetite)
- Diarrhoea
- Tremor, Palpitations
- Diaphoresis (sweating)
- Lid retraction & Lid Lag (thyroid stare)
- Proptosis (Exophthalmos): bulging eyeball, more common if smoke
- Menstrual irregularity
- Goitre
- Tachycardia
45
Q
Thyroid associated eye disease (Exophthalmos)
A
- Lateral flare
- Conjunctival redness and chemosis
- Conjunctival oedema
- Increases scleral show upper eyelid retraction
- Thickened brow
- Puffy lower lids
- Lower eyelid retraction/displacement
- Lid lag
46
Q
Investigations of Graves
A
- Low TSH High Free T3 and Free T4
- Thyroid antibodies (TBII / TRAb): confirms
- Radionucleotide thyroid scan
- Thyroid associated eye disease: lid lag
47
Q
Hyperthyroidism treatment
A
- AntiThyroid Drugs: Carbimazole, Propylthiouracil, Alert the patient about agranulocytosis (low neutrophils)- if they have sore throat stop Carbimazole and go to GP to get FBC
- Definitive Treatment: Radioactive iodine, Surgery - Thyroidectomy
48
Q
Radio-iodine therapy
A
- Shared decision with patient – Counsel and consent
- Oral- Fixed dose of Radioiodine 131I
- Medical Physics
- Away from people for specific period: especially children and pregnant women. Cant do if trying for children in either man or women
- Post Radioiodine Hypothyroid: will need replacement Levothyroxine
49
Q
Subclinical hypo and hyperthyroid
A
- Subclinical hypothyroid: Elevated TSH with normal free T3 and free T4
- Subclinical hyperthyroid: Suppressed TSH with normal free T3 and free T4
