|Hypothyroidism BMJ 2008;337:a801|
|Coarse facies – dry thickened skin on face and hands, puffy eyes, sparse hair on scalp with loss of outer 1/3 eyebrows
Slow croaky monotonous speech
Slow pulse, slow ankle jerks
|Commonest cause in the West is autoimmune Hashimoto’s
Patients almost always test positive for anti-thyroid peroxidase (anti-TPO) and antithyroglobulin antibodies
|low T4 with normal TSH
due to pituitary failure
|Subclinical hypothyroidismbmj/337/bmj.a834||Normal free T3 and T4, but elevated TSH.Common condition, affecting about 5-10% of women over the age of 50.Thyroxine should be started if:
Positive anti-TPO or antithyroglobulin antibodies – most will develop overt hypothyroidism eventually.The patient has been treated for Graves’ disease in the past.The patient has another organ-specific autoimmune disease.The TSH is >10 mU/l.If the patient does not fall into any of the above groups, they should have TFTs repeated every 6 months; there is very little evidence to suggest that they will benefit from thyroxine, and the risks of osteoporosis and atrial fibrillation from unnecessary treatment should be borne in mind.
However, a trial of thyroxine could be considered
if patient symptomatic,
if the TSH is rising,
if strong FH of thyroid disease
if the patient has a goitre
The aim of treatment is to keep the TSH within the normal range
Levothyroxine 50-100 mcg od, before breakfast, adjusted in 50cg steps every 3-4 weeks until normal metabolism maintained
(usual maintainance 100-150 mcg od – 200mcg if obese).
In cardiac disease, severe hypothyroidism, and patients over 50 years, should be introduced at 25micrograms once daily, adjusted in steps of 25 mcg every 4 weeks according to response; usual maintenance dose
After changes in dose of thyroxine, thyroid function tests should normally be repeated after approximately 8 weeks allowing steady state to be achieved. The total daily dose can usually be administered as a single dose in the morning.
It takes 6-8 weeks for the thyroid stimulating hormone (TSH) to change in response to an alteration in dosage.
Many patients don’t feel the benefit of treatment for 3 months after thyroxine is started, and complete recovery can take up to 12 months.
Once the patient is stable, their thyroid function should be checked annually.
The aim should be to keep restore free T4/T3 and TSH within the normal range, (TSH ideally around 1 mU/l)
|TREATMENT-INDUCED TSH SUPPRESSION|
|Some patients feel very well on a dose of thyroxine that keeps the free T4 and T3 within the normal range, but causes the TSH to become suppressed.
Ideally, dose reduction should be attempted, but a proportion of these people will then become symptomatic and may need to stay on the higher dose.
There are potential harmful effects involved in treating patients in this way; there is some evidence that TSH suppression has an adverse effect on bone mass in postmenopausal women and that there is an increased incidence of atrial fibrillation. It is therefore advisable to exclude osteoporosis by ordering a DEXA scan, which may need to be repeated at regular intervals if there is an initial abnormality.
|Reduce dose if:
patient develops new-onset AF, angina or heart failure
patient develops osteoporosis
serum T3 concentration is raised.
|autoimmune condition more common in women 40-60.
Most patients will have TSH-receptor antibodies which bind to and stimulate the TSH receptor with a prolonged stimulatory action (LATS)70-80% will be positive for anti-TPO antibodiesMore common in females (8:1).
Hyperkinesia restlessness and fidgeting.
Prominent eyeballs (exopthalmos), lid retraction (staring eyes visible sclera and wide palpebral fissure) and lid lag (delayed movement of upper lid)
May be opthalmaplegia and diplopia, grittiness, discomfort
May be goitre +/- bruit.
Tachycardia (+/- arrythmia AF, ST, SVT, VEBs)
Fine tremor, hot sweaty palms
pretibial myxoedema (thick raised mauve plaques with peau d’orange appearance over shins and feet)
shoulder muscle wasting (thyrotoxic myopathy- difficulty rising from chair)
Firm, smooth diffuse goitre
|Secondary hyperthyroidism in already hyperplastic gland.
Predominance of CVS symptoms AF, heart failure
|>eg TSH-producing pituitary adenoma|
|Thyroiditis||Painful form usually viral
Painless especially in the postpartum period.
t3 thyrotoxicosis = normal plasma levels of thyroxine T4 but raised triiodothyronine T3. Clinically identical
|Referral||Hyperthyroidism should usually be referred to a secondary care facility to initiate treatment, as management options might include radioiodine treatment.
Initial GP investigations might include LATS antibodies and ultrasound
|Carbimazole||tablets 5mg, 20mg
Dose: 15-40mg daily, maintained until patient becomes euthyroid, usually 4-8 weeks; the dose may then be progressively reduced to a maintenance of 5-15mg daily.During carbimazole treatment, patients should be advised to report signs and symptoms of infection, especially sore throat, which may indicate bone marrow suppression.
If sensitivity (eg rash) occurs with carbimazole then propylthiouracil is an alternative.
|Propylthiouracil||tablets 50mg Dose: 200 – 400mg daily.
Maintain this dose until the patient becomes euthyroid.
The dose may then be gradually reduced to a maintenance dose of 50 to 150mg daily
|Beta blockers||Adjunct for relief of thyrotoxic symptomsNadolol tablets 40mg, 80mg Dose 80-160mg odPropranolol m/r capsules 80mg and 160mg
Dose 80mg od increased as necessary to 240mg dailySome patients may require doses up to 320mg daily (unlicensed)Nadolol produces a more reliable response, it is water soluble and is excreted unchanged.Note that carbimazole and levothyroxine can be given concomitantly in a blocking-replacement regimen, although this is NOT suitable during pregnancy.
Midline swelling, moves with swallowing
Retrosternal extension, thyroid bruit
moves with tongue protrusion only = thyroglossal cyst
Neck, eyes, pulse, tremor, skin/hair
Proximal myopathy; reflexes
|Patients are at increased risk of thyroid disease|
|Patients on lithium and amiodarone should have 6mly TFTs|
|Women with type 1 diabetes should have TFTs checked in the first trimester of pregnancy and post-delivery (high risk of postpartum thyroid dysfunction)|
|People with Down’s syndrome, Turner’s syndrome and Addison’s disease should have annual checks, as they are at risk of developing hypothyroidism.|
|Diabetic patients should also have an annual TFT check|
|Patients with AF should have a one-off test to exclude hyperthyroidism.|
|Patients with hyperlipidaemia and macrocytosis should also be tested as a one-off, to exclude underlying hypothyroidism|
4 glands from 4th (and 3rd) branchial arch 40 mg in wt 40mm in diameter
|Primary|| Increased secretion of parathyroid hormone PTH from parathyroid adneoma(s), hyperplasia or rarely carcinomaMay be mild asymptomatic hypercalcaemia orpolyuria and polydypsia
|Secondary||Increased PTH secretion in response to hypocalcaemia (CKD, Vit D deficiency)signs and symtoms of hypocalcaemia +/- the underlying cause|
|Tertiary||autonomous PTH secretion following chronic secondary hyperparathyroidism.|
|Secondary hyperparathyroidism 10 Cs|
|cranial pressure raised|
- Post thyroidectomy or parathyroidectomy
- iron overload
- Wilsons Disease
|Anterior Pituitary||Posterior Pituitary|
|those giant gonads prolong the action
produced in the hypothalamus
Prolactinomas NEJM 2010;362:1219
|Acromegaly / gigantism|
|Big boggy hands|
|DM / glycosuria|
|Enlarged tongue heart and throat|
|Fields (bitemporal hemianopia)|
|Gynaecomastica galactorrhoea greasy skin|
|Increasing shoe/ring/dentures/ size|
|Jaw enlargement and prognathism|
Excess GH secretion (> 10ng/ml fasting) from acidophilic or less commonly chromophobic adenoma (rarely histologically normal pituitary) causing excess growth of viscera, bones, soft tissuesof the hand, supraorbital ridges, sinuses and lower jaw.
May present with: headaches, visual disturbance, paraesthesia in hands and feet, change in hat ring or shoe size, arthralgia, sweating, DM or hypertension.
Presents like DM with polydypsia and polyuria.
May be cranial (head injury, pituitary tumours and infiltrations, meningitis and encephalitis, strokes, idiopathic and familial) or nephrogenic (CKD, lithium, electrolyte disturbance, or familal)
– exclude other causes of polydisia and polyuria ( DM, hypercalcaemia, CRF, diuretic abuse, psychogenic)
– check glucose, electrolytes, Ca, U&E, plasma and urine osmolarity. (Nigh Na increased plasma osmolarity but low urine osmlolarity)
– water deprivation test
– CXR – sarcoid TB
Ca Bronchus kidney brain tumour lymphoma
bronchiectasis atypical Pneumonia
chemotherapy – vincristine cyclophosphamide
Inappropriate salt excretion in prescence of hyponatraemia
Symptoms – fatigue, anorexia and weight loss.
low plasma sodium and plasma osmolality
inappropriately high urine osmolality (1.2-2x plasma)
high urine Na > 20 mmol/l
urine volume 0.5-1.5l per 24hrs
normal renal, adrenal and thyroid function
|Cushings Glucocorticoid excess|
|ACTH dependant||ACTH independant|
|Hypersecretion of adrenal glucocorticosteroids
– bilateral adrenal hyperplasia due to ACTH from pituitary adenoma
– or rarely paraneoplastic syndrone
|Glucocorticoid secreting primary adrenal tumouralso long term steroid use
ACTH levels suppressed – no pigmentation
Moon shaped round plethoric face.
Buffalo hump due to prominent supreaclavicular and dorsal cervical fat pads.
Purple abdominal striae.
Purpura and spontaneous bruises over extremeties
Acne and hirsuites
24 hr urinary cortisol
9 am cortisol
Dexamethasone suppression test
Excess autonomous mineralocorticoid/aldosterone production from adrenal adenoma with suppression of renin – Conns syndrome (also rarely Ca or Bilateral adrenal hyperplasia).
Causes renal sodium retention, K and H+ loss — hypertension, hypokalaemia, metabloic alkalosis.
Renal hypoperfusion (RAS, heart failure, cirrhosis) causing raised renin levels (also rarely Renin producing tumour)
bilateral hemorrhage into the adrenal glands in meningococcal septicaemia leading to adrenal insufficiency
Primary adrenal failure – Addisons – glucocorticoid and mineralocorticoid deficiency
Secondary adrenal failure – isolated ACTH deficiency in pituitary disease
causes glucocorticoid deficiency only
- Infiltrations – amyloid haematochromatosis
- Infections – TB fungi
- Haemorrhage – anticoagulants, meningococcal septicaemia
- Adrenal Mets
Hypotension, hyponatraemia, hypokalaemic acidosis.
Pigmentation in buccal mucosa, scar tissue, and palmar crease due to xs ACTH
Other causes of buccal pigmentation
Peutz-Jegher syndrome – AD + multiple small intestine polyps
Seen in known cases of Addisons and meningococcal septicaemia.
Give IV hydrocortisone 100mg dextrose saline (taking blood for baseline electrolytes) and transfer ITU.
|10% adrenal / bilateral|
|10% extra adrenal|
|10% in children|
|10% in children|
Episodes of palpitations, sweating, pallor headache associted with marked hypertension.
Catecholamine producing tumour of adrenal medulla.
Diagnosed by raised 24 hr urinary catecholamines.
May be part of Multiple endocrine neoplasia syndrome, Von Hippel Lindau and neurofibromatosis
pancreatictumours gastrinoma insulinoma
pituitary adenomas – prolactinoma acromegaly
Thyroid– medullary ca
Parathyroid – primary hyperparathyroidism
|Incompetent tricuspid / pulmonary valves|
|Indoles in stool|
Facial flushing esp after alcohol /spicy food, diarrhoea. Symptoms suggest liver involvement.
Due to neuroendocrine tumour secreting serotonin and tachykinins usulally in the intestine, occ in the lung.
Rised 24 hr urinary 5 hydroxyindole acetic acid (5 HIAA) a serotonin metabolite and plasma chromogranin A.
Autosomal Recessive enzyme defects affecting synthesis of steroid hormones
eg 21 alpha hydroxylase deficiency
Cortisol deficiency (addisonian crisis)
Aldosterone deficiency (sodium loss and hypotension)
ACTH oversecretion then excess production of 17 OH progesterone – causing virilisation.
or 11 beta hydroxylase deficiency
increased androgens causing virilistion
increased coticosterone and hypertension