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
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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
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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
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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

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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
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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
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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
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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
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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
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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
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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)

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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
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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
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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
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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)
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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)
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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).
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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)
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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
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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