Thyroid Examination

Goitre and Graves Disease

General appearance
  • Overweight versus underweight
  • Obvious exophthalmos
  • Alopecia
  • Eye-brow wasting
  • Presence of goitre
  • Presence of thyroidectomy scar
  • Movement of goitre with swallowing
  • No movement with tongue protrusion (compared to thyroglossal cyst)
  • Stridor
  • Cerebellar ataxia - hypothyroidism
Hands
  • Onycholysis
  • Thyroid acropachy (like clubbing, but caused by subperiosteal new bone formation)
  • Palmar erythema
  • Diaphoresis
  • Dry skin
  • Cold to touch/ warm to touch
  • Tachycardia vs bradycardia
  • Atrial fibrillation
  • Hypertension
  • Fine tremor
  • Carpal tunnel syndrome
Arms
  • Proximal myopathy
Head
  • Proptosis
  • Exophthalmos
  • Lid lag
  • Lid retraction
  • Thinning of eyebrows
  • Congestive oculopathy
  • Diplopia
  • Decreased visual acuity
  • Horner’s syndrome
Neck
  • Goitre
  • Red skin overlying goitre in grave’s disease (Maranon’s sign)
  • Pemberton’s sign
  • Tracheal deviation
  • Cervical lymphadenopathy
  • Movement of mass with swallowing
  • Thyrotoxic bruit
Chest
  • Pleural effusion
Legs
  • Pre-tibial myxoedema
  • Reflexes - impaired relaxation phase of deep tendon refflexes
 
What is the differential diagnosis of a central neck mass?
  • Multinodular goitre
  • Diffuse goitre
  • Lymphoma
  • Thyroid cancer
  • Thyroglossal cyst
  • Lymphadenopathy
  • Carotid artery aneurysm
  • Branchial abnormalities (cysts, sinuses and fistulae)

What is the differential diagnosis of proptosis
  • Graves orbitopathy
  • Cavernous sinus thrombosis
  • Fistula between the carotid artery and the cavenous sinus
  • Retro-orbital tumour (lymphoma etc)
  • Abscess
 
What investigations would you perform?
  • Most pertinent investigations would be TFTs to determine functional status
  • Thyroid antibodies, especially anti TPO, anti TG, TRAB (for graves)
  • Thyroid ultrasound
  • Thyroid nuclear medicine scan (to determine if lesion is hot or cold)
  • FNA if indicated (look at cytology for risk features, if follicular, need to go to surgery because a follicular malignancy can only be diagnosed if there is vascular or capsular extension)
 
What are the causes of painful thyroid swelling?
  • Infective thyroiditis – usually suppurative
  • Subacute granulomatous thyroiditis
  • Radiation thyroiditis
  • Compare this to painless swelling which is hashimoto’s or lymphocytic thyroiditis, post-partum thyroiditis, graves disease, iodine deficiency, diffuse multinodular goitre, thyroid cysts
 
What are the clinical signs of hypothyroidism?
  • Slow, slurred speech
  • Bradykinetic walk
  • Overweight
  • Hoarse, croaking voice
  • Bradycardia
  • Subcutaneous oedema owing to deposition of glycosaminoglycan in the dermal layer
  • Periorbital swelling
  • Proximal myopathy

What is the mechanism behind orbital oedema in grave's disease?
  • infiltration of glycosaminoglycans into the extra-ocular muscles causes a raised orbital pressure
  • This then causes obstruction on the superior ophthalmic vein, leading to congestion and subsequent oedema
  • Conjunctival oedema is manifested as chemosis

What are the eye findings in grave's disease?
  • peri-orbital oedema
  • chemosis due to orbital compression
  • proptosis
  • exopthalmos (defined only when you see inferior sclerae when eye is in neutral position)
  • exposure keratitis
  • opthalmoplegia with diplopia (especially to inferior rectus and medial rectus muscles)
  • decreased visual acuity and relative afferent pupillary defect
  • lid lag
  • lid retraction (due to sympathetic hyperactivity as a result of over-activity of muller's muscle)

Acromegaly

Dermatological manifestations
  • sweating is an important sign as it suggests that the disease process is active
  • doughy, thickened skin, best felt over the dorsum of the hand
  • enlarged pores
  • skin tags, known as molluscum fibrosum, around the axillae
  • acanthosis nigricans
  • thickened and hardened nails
  • hypertrichosis
Hands
  • large spade like hands with spatulate fingers
Face
  • Coarse facial feaures
  • facial wrinkles
  • frontal bossing
  • enlargement of the nose
  • prognathism - overbite
  • macroglossia
Other
  • gynecomastia
  • bitemporal hemianopia (seen in 10%)
  • optic atrophy, angioid streaks which are red, brown, grey streaks larger than the diameter of the retinal veins that appear to emanate from optic disc
  • carpal tunnel syndrome
  • hypertension
  • cardiomegaly and congestive cardiac failure
  • diabetes
  • arthropathy
  • look for evidence of pituitary insufficiency

What is the unique association with skin tags in patients with acromegaly?
  • presence of skin tags are known to correlate with presence of colonic polyps

What is the medical work-up of a patient suspected to have acromegaly?
  • Hormonal
    • IGF-1, lab specific and age corrected, no variation with meals, but false positives and negatives exist
    • OGTT --> 75g load, then GH every 30min for 2h, normal response is to suppress and will be <1ng/ml, in acromegaly can inc, dec or no change but will NOT suppress <1ng/ml
    • Don’t ever do random GH level
  • Structural --> MRI
  • Assess end-organ damage --> ECHO, ECG, visual fields, sleep study, other pit hormones, colonoscopy

How do you treat acromegaly?
  • Surgical first --> transphenoidal, with 24hr post-op GH <1ng/ml 98% predictive of cure, low mortality 1%
  • Medical --> somatostatin receptor ligands: longer acting, inhibit GH secretion, octreotide, lantreotide, pasireotide.
    • Ideal to have high affinity for subtype 5 receptor which is what pasireotide does. SE = gallstones/ sludge
    • New Rx = pegvisomant --> prevents dimerization of GH R --> prevents IGF-1 production, use in addition to uncontrolled GH release in somatostatin Rx pts
    • Dopamine agonists cabergoline and bromocriptine can be used as they suppress GH release
  • Monitoring response --> difficult to assess: normalization of IGF-1 or OGTT <1ng/ml
  • Follow-up --> Life long f/u, aggressive Rx of metabolic RF, GH level is the single most important determinant of mortality in acromegaly​

Cushing's examination

General inspection
  • Flat mental affect
  • Moon like facies
  • dorso-cervical fat pad
  • supra-clavicular fat pad
  • extensive pigmentation secondary to raised ACTH levels
  • central/ truncal obesity with thin limbs
  • Evidence of acne vulgaris
Face
  • Bitemporal hemianopia secondary to optic chiasm lesion (pituitary macroadenoma)
  • telangiectasia
  • acne vulgaris
  • cataracts
  • plethora
  • fundoscopy reveals hypertensive changes
Back
  • kyphosis
Arms
  • evidence of proximal myopathy
  • brusing, thin skin
  • hypertension on measuring blood pressure
  • evidence of fungal infections
  • acanthosis nigricans secondary to insulin resistance
  • skin tags secondary to insulin resistance
  • hirsuitism
Legs
  • proximal myopathy, may also be exacerbated by hypokalaemia (as cortisol also has mineralocorticoid receptor tropism)
  • pitting oedema secondary to fluid retention
  • ask to examine hip joint for evidence of avascular necrosis of the hip
Abdomen
  • central adiposity
  • violaceous striae
  • evidence of bilateral adrenelectomy scars (this was a historical treatment for cushings disease prior to transphenoidal surgery) - retroperitoneal approach is the most common therefore scars at the neck

Difference between cushing's syndrome and cushing's disease
  • Cushing's disease is related to hypersecretion of ACTH by a pituitary tumour
  • Cushing's syndrome refers to symptoms and signs caused by states of cortisol excess

What are the major causes of cushing's syndrome?
  • Most commonly exogenous steroid use
  • Cushing's disease (66%)
  • adrenal adenoma > ectopic ACTH > adrenal carcinoma > nodular adrenal hyperplasia

What is the diagnostic work-up for someone that you suspect has cushing's syndrome?
  • First confirm hormone excess
    • there are lots of difficulty and controversy
    • Screening tests (1) 24hr urine free cortisol [look for >3x, if not >3x then need to re-test] (2) late night cortisol = loss of diurnal variation (3) overnight dexamethasone suppression test = impaired corticosteroid negative feedback + dexamethasone does not interfere with assay
    • Confirmatory tests [can repeat or do two diff ones as per MKSAP] (1) 24hr urine cortisol (2) o/n DM suppression test [give 1mg 2300, take cortisol 0800, suppress to <50]
  • Differentiate cause:
    • Plasma ACTH [low --> adrenal; high --> pituitary, ectopic, v high --> ectopic]
    • High dose DMS test --> suppresses cushings disease ~ >90% supression, not ectopic ACTH. However, suppression does occur in 10 - 25% of patients with ectopic ACTH secretion. 
    • Dexamethasone infusion test --> as above
    • Petrosal sampling, basal and after CRH. If 1.5:1 grad pre, then 3:1 post CRH, then pit source, may lateralise. Especially if there is diagnostic uncertainty
    • Localise: MRI, CXR, CT adrenals

What is the management?
  • If adrenal --> surgery
  • Pituitary --> surgery + replacement therapy VS pasireotide
  • Ectopic -->  Sx if possible, consider adrenelectomy, also medical Rx: ketoconazole

Panhypopituitarism

Clinical findings:
  • Case is usually a secondary hypopituitarism, either secondary to a non secreting adenoma or surgical resection
  • Evidence of local mass effect
    • bi-temporal hemianopia
    • unlikely to have papilloedema 
    • decrease in visual acuity
    • always ask for formal perimetry
    • tumour may extend to the cavernous sinus affecting nerves III, IV, V(1 and 2), VI
  • Evidence of lack of hormone
    • ACTH and corticosteroid lack: postural hypotension as glucocorticoids help maintain vascular tone, pale dry 'alabaster skin' because of the inability to tan due to lack of MSH (from POMC --> MSH + ACTH)
    • TSH deficiency: evidence of hypothyroidism
    • gonadotropin deficiency: decrease in secondary sexual characteristics with decrease in muscle bulk, loss of axillary hair etc
  • Evidence of previous hormone excess prior to surgery
    • GH excess with acromegaly
    • Cushing's disease
    • prolactinoma with galactorrhoea

What are the causes of hypopituitarism?
  • Vascular: pituitary infarction, shehans syndrome, pituitary apoplexy
  • Infection/ Inflammation: brain abscess, IgG4 related disease, ipilumimab induced hypophysitis
  • Trauma
  • Auto-immune: auto-immune hypophysitis
  • Metabolic: nil
  • Idiopathic/ Iatrogenic: post surgery/ radiotherapy/ drugs such as ipilumimab
  • Neoplastic: pituitary mass
  • Degenerative
  • Congenital: empty sella syndrome

Comment on the relative potencies of the glucocorticoid preparations
  • Comes in 5 preparations: hydrocortisone, cortisone, prednisolone, dexamethasone, fludrocortisone
  • Highest potency = dexamethasone, fludrocortisone has highest mineralocorticoid potency
  • Prednisone has 4x potency of hydrocortisone, therefore 5mg pred = 20mg hydrocort
  • Dexa has 30 – 40x potency of hydrocort, 30mg of hydrocort = 0.75mg dex

How would you manage a patient with pan-hypopituitarism prior to surgery?
  • Minor Sx --> usual AM dose
  • Major Sx --> usual AM dose + 100mg prior to Sx + 50 TDS for 24hrs + taper 50% each day
  • Double HC dose if unwell [however tell patient 3 x 3 rule, triple dose for three days], if v unwell, increase 3-4x, parental treatment if there is nausea or vomiting