20 - Thyroid and Adrenal Endocrinology Flashcards
What is the difference between primary and secondary gland failure?
Primary: end organ hormone low but pituitary hormone high
Secondary: end organ hormone high and pituitary hormone low
So the primary gland would be the one at the end of the cascade
What structures lie close to the thyroid gland?
- Parathyroid glands posteriorly
- Superior and inferior thyroid arteries
- Recurrent laryngeal nerve
What is a thyroglossal cyst and how can you tell it is a thyroid lump on examination?
Thyroid starts in the base of the tongue and travels down. Some remnant tissue can be left behind on the travels forming a cyst
Lump will move up with swallowing and sticking tongue out
What cells are present in the thyroid and what is their role?
Follicular cells: Synthesise thyroglobulin which is then iodinated to form thyroxine which is stored in the…
colloid: Thyroid tissue is made up of a substance called colloid
C-Cells/Neuroendocrine cells: Secrete calcitonin
Main cells are follicular and C-cells
What malignancy causes high calcitonin levels?
Medullary thyroid cancer
Thyroid hormone is made from iodinated tyrosine. What do they bind to travel in the blood?
Carried by the following to nuclear receptors:
- TBG
- Albumin
- Transthyretin
How do you do a thyroid examination?
1. General Inspection: agitated, fidgety
2. Hands: peripheral tremor paper, pulse rate and rhythm
3. Face: inspect eyebrows/skin/sweating, exopthalmous, eye movements, lid lag
4. Thyroid: inspect, swallow water, protrude tongue, palpate
5. Lymph nodes
6. Trachea: deviation in goitre
7. Percuss: retrosternal dullness
8. Auscultate: bruits in Grave’s
9. Special Tests: biceps, pretibial myxedema, proximal myopathy
What is included in a TFT panel, and what can affect this panel?
- TSH
- Free T3 and T4
Amount of TBG. More TBG can increase total T3/T4 but doesn’t mean free T3/T4 has increased!!!
Pregnancy, Illness, Lithium and Amiodarone can derange TFTs so do TFTs on relatively well person
What thyroid tests should you look at for hyperthyroidism and what will they show?
T3, T4, TSH
Primary Hyperthyroidism (issue with thyroid): Low TSH, Raised T3 and Raised T4
Secondary Hyperthyroidism (thyroid being stimulated): Raised TSH, Raised T3 and Raised T4. This is rare and often due to TSH secreting pituitary adenoma
What thyroid tests should you look at for hypothyroidism and what will they show?
TSH and only T4
Primary Hypothyroidism (autoimmune): raised TSH, low T4
Secondary Hypothyroidism (pituitary issue): low TSH, low T4
Apart from a standard TFT panel, what other investigations can you do for thyroid pathology?
- Thyroid autoantibodies e.g TPO, anti-TSH, anti-TG
- Serum thyroglobulin
- US
- Scintigraphy
What are some signs and symptoms of hyperthyroidism (a.k.a thyrotoxicosis)?
Due to increased sympathetic action
Symptoms: weight loss, insomnia, irritability, anxiety, heat intolerance, palpitations, tremor, diarrhoea, sweating, oligomenorrhea, infertility
Signs: sinus tachycardia, AF, fine tremor, palmar erythema, thin hair, lid lag due to increased sympathetic tone, hyperreflexia, goitre, bruits
How may hyperthyroidism present differently in the elderly and children?
Elderly: paradoxically with reduced energy levels, known as apathetic thyrotoxicosis
Children: typical symptoms plus accelerated growth and behavioural disturbance
What are some of the signs of hyperthyroidism due to Grave’s disease?
Due to cross reactivity with TSH receptors in back of orbit and skin
- Eyes: lid retraction, exophthalmos, opthalmoplegia
- Pretibial myxoedema: above lateral malleoli
- Thyroid acropachy: clubbing, painful toe and finger swelling
- Goitre
What are some of the different causes of hyperthyroidism?
Grave’s (most common): autoimmune, usually women 40-60, IgG antibodies that can stimulate TSH receptors in thyroid, orbit and skin. Associated with other autoimmune conditions and can be triggered by stress, infection, pregnancy
Nodular Hyperthyroidism: can be toxic adenoma or toxic multinodular goitre that releases T3/T4. More in elderly than Grave’s
Ectopic Thyroid tissue: metastatic follicular thyroid cancer, struma ovarii
Thyroiditis: inflammation of thyroid due to viral infection, child birth or medication like amiodarone
What autoantibody is present in Grave’s disease?
TSH receptor autoantibody (stimulates TSH)
What investigations should you do to diagnose hyperthyroidism and find the underlying cause? What do these tests show?
TFTs: low TSH, raised free T3/T4
Thyroid autoantibodies: TPO, TSHrAB
Bloods: normocytic anaemia, raised Ca, raised LFTs, raised ESR, neutropenia in Grave’s
US: for nodular disease
Isotope Scan (Te/Iodine): Grave’s will have uniform uptake, nodular disease will only have increased uptake in nodular areas, thyroiditis will not have uptake
What is subclinical hyperthyroidism and how is it managed?
Low TSH
Normal T3/T4
Only treat if symptoms
What are the different treatment options for hyperthyroidism?
Medical (1st Line)
- Thionamides: carbimazole and propylthiouracil
- Beta-blockers: propanolol to control symptoms rapidly
Surgical:
- Thyroidectomy
Radioactive Iodine:
- Single dose of I-131
How do you start someone on Carbimazole for hyperthyroidism?
Two methods:
Titration: Take 20-40mg/day for 4 weeks then titrate according to TFTs
Block-Replace: Give carbimazole-levothyroxine simultaneously to prevent iatrogenic hypothyroidism.
If Grave’s keep on for 12-18 months then withdraw. If relapse need surgery or radioactive iodine
What do you need to warn people about when starting them on carbimazole? (Thionamide)
- Will take 4-6 weeks to normalise thyroid levels
- Risk of agranulocytosis (bone marrow suppression) (If unexplained fever/sore throat need urgent FBC to exclude pancytopenia. Stop drug if neutrophils low)
- May get generalised rash but will stop when stop taking drug
The definitive treatment of hyperthyroidism is radioactive iodine or surgery, driven by patient choice. What are the disadvantages of radioactive iodine?
I131
- Contraindications: pregnancy and lactation
- Can flare up eye disease
- Common post-treatment hypothyroidism that needs lifetime levothyroxine
- Patient emits small amount of radiation after so needs to avoid pregnant people and children for a few weeks
What are the complications of thyroidectomy surgery used to treat hyperthyroidism?
- Hoarse voice if damage recurrent laryngeal nerve
- Bleeding
- Infection
- Hypoparathyroidism so low Ca
Control thyroid before surgery and use beta-blockade during anaesthetic induction to prevent peri-op AF
What are some of the complications of hyperthyroidism that is left untreated or poorly treated?
- Heart failure
- Angina
- AF
- Osteoporosis
- Opthalmopathy
- Gynaecomastia
- Thyroid storm
What are some signs and symptoms of thyroid eye disease?
Symptoms: eye discomfort, incresed tear production, photophovia, diplopia
Signs: exophthalmos, proptosis, papilloedema, opthalmoplegia
How is thyroid eye disease managed?
- Control hyper/hypothyroidism
- Stop smoking (biggest risk factor)
- Artificial tears
- High dose steroids if severe
- Surgical decompression if severe
What are some causes of a goitre?
What are some signs and symptoms of hypothyroidism?
Symptoms (similar to depression): weight gain, constipation, fatigue, cold intolerance, menorraghia, poor memory
Signs: bradycardia, hyporeflexia, dry skin, non-pitting oedem, round puffy face, thickening of skin
Often subtle signs/symptoms and diagnosed incidentally
What are some of the causes of hypothyroidism?
Primary (high TSH)
- Hashimotos: commoner in women
- Iodine deficiency!!!!!!!!
- Drug induced: anti-thyroid drugs, amiodarone, lithium, iodine
- Post thyroidectomy/Iodine treatment/Radiation Therapy
- Pregnancy induced
Secondary: (low TSH)
- Hypopituitarism: low fT4 and low TSH, investigate pituitary
What autoantibodies are present in Hashimoto’s disease?
TPO: thyroid peroxidase antibodies
TG: antithyroglobulin
What are some causes of hypothyroidism in neonates/infancy?
Iodine deficiency: causes severe mental retardation (cretinism)
Familial thyroid dyshormonogenesis: autosomal recessive defect in thyroid hormone synthesis
What are some investigations done to diagnose hypothyroidism and what do they show?
TFTs: high TSH (low in secondary), low fT4
TPO: diagnoses autoimmune hypothyrodism
Triglycerides/Cholesterol: raised
How is hypothyroidism treated?
LEVOTHYROXINE
- Starting dose usually 50-100ug, if elderly or IHD then 25ug
- Check TSH at 4 weeks on blood test
- Want TSH to be normal not suppressed
- If secondary then get T4 to upper normal because cannot rely on TSH
- Once right levels check TSH yearly
When someone is being treated with levothyroxine, what are the causes of a persistently high TSH or suppressed TSH?
- Persistently high (underreplacement)
- Poor compliance
- Malabsorption (Crohn’s, PPI)
- Suppressed (overreplaceement)
What are the risks of over replacement with levothyroxine?
- AF
- Osteoporosis
Why can amiodarone cause thyroid issues?
Iodine rich drug that is structurally like T4
- Hypothyrodism: iodine excess
- Hyperthyroidism: destructive thyroiditis causing hormone release
Check TFTs 6 monthly on Amiodarone
What is subclinical hypothyroidism and how is it managed?
- Elevated TSH but normal T3/T4
- If asymptomatic do not treat as often spontaneously resolves
- If TSH>10 and asymptomatic start treatment as high risk of progression
- If planning pregnancy or symptomatic start treatment
- If positive thyroid antibodies check TFTs yearly
What are some signs and symptoms of a thyrotoxic crisis?
Lifethreatening hypermetabolic state by excess release of thyroid hormone
- Agitation
- Confusion
- Coma
- Tachycardia
- Hypertension
- AF
- Acue abdomen
- Heart failure
What are some triggers of a thyrotoxic crisis?
- Untreated hyperthyroidism
- Recent thyroid surgery or radioiodine
- Infection
- MI
- Trauma
A thyrotoxic crisis can lead to heart failure and pulmonary oedema. How is a thyrotoxic crisis managed?
Start treatment before test results!!!
- Counteract peripheral effects of thyroid hormones
- Inhibit thyroid hormone synthesis
- Treat systemic complications
What pattern is cortisol released in and what is it carried by in the blood?
- Highest at 8am, lowest at midnight. Therefore get early morning sample
- Carried by CBG and albumin
- Anything that increases CBG (e.g oestrogen) may increase total cortisol but doesn’t increase free cortisol
What are the causes of primary and secondary adrenal insufficiency?
Primary (destruction of whole of adrenal gland/defect in synthesis)
- Addison’s disease (autoimmune)
- TB
- Adrenal metastases
Secondary
- Long term steroids (only symptoms when withdrawal)
- ## Pituitary issues
What are some symptoms of Addison’s disease? (primary adrenal insufficiency)
Often non specific and gradual onset:
- Fatigue and weakness
- Anorexia
- Weight loss
- Nasea
- Abdominal pain
- Increased pigmentation
- Mineralcorticoid deficiency: postural hypotension/dizzy
- Glucocorticoid deficiency: hypoglycaemia
- Androgen deficiency: reduced libido, loss of pubic/axillary hair
What are some confirmatory and supportive investigations done to diagnose Addison’s disease?
Supportive:
- U+Es: hypoNa, hyperK, raised urea due to low aldosterone
- Hypoglycaemia due to low cortisol
- Anaemia
Confirmatory:
- Low 9am cortisol but raised ACTH
- Synacthen stimulation test: 30min cortisol >550 then can exclude Addison’s
What is a Synacthen Test?
Do plasma cortisol before and 30 min after 250 mcg IM administration of ACTH
Should produce an increase in cortisol >550 if normal, if this does not occur can diagnose Addison’s
What advice do you need to give patients when starting them on treatment for Addison’s disease?
- Double dose of steroids when ill until illness has resolved
- Need to get IV or IM glucocorticoids if vomiting/diarrhoea
- Give emergency number for endocrine team
- Steroid emergency card
How may a patient in an Addisonian crisis present and what are some causes of this?
Background of Addison’s:
- Shock (tachycardia, low BP, raised HR, oliguria)
- Hypoglycaemia
Causes: forgotten to take long term steroid, not increased steroids in period of illness/surgery, bilateral adrenal haemorrhage (meningococcaemia)
An Addisonian crisis can be fatal, how is this treated?
Bloods: ACTH, Cortisol, U+Es
Cultures: if think infection has triggered, e.g bloods, sputum
START TREATMENT STRAIGHT AFTER TAKING BLOODS
- Hydrocortisone 100mg IV
- IV fluid boluses to support BP
- Monitor blood glucose for hypoglycaemia and correct
When should you consider Conn’s syndrome as a diagnosis, and what do you find on investigations?
- Hypokalaemia
- Low renin
- High aldosterone levels
- CT/MRI may show adenoma
What are phaeochromocytomas and paragangliomas?
Rare catecholamine producing tumours that arise from chromaffin cells, usually in the adrenal medulla (phaeochromocytoma) or extra-adrenal chromaffin tissue near blood vessels (paragangliomas)
Highly familial, especially in bilateral, extraadrenal malignant tumours
What are some of the clinical features of a phaeochromocytoma and why are they so dangerous left untreated?
Classic triad: episodic headache, sweating, tachycardia
Other symptoms: palpitations, hypertension, diziness, panic attacks/anxiety, pallor
If left untreated can cause hypertensive crisis, encephalopathy, hyperglycaemia, pulmonary oedema, cardiac arrhythmias and death!!!!!
What investigations should you do if you suspect phaeochromocytoma?
- 24H urine metanephrines and catecholamines
- Plasma metanephrines
- Localisation of tumour with abdominal CT/MRI
- If cannot find then do whole body MRI
- MIBG scan (chromaffin seeking isotope) or PET scan to rule out metastases
When should you do genetic testing for phaeochromocytomas and what should be done if there is a mutation found?
Genetic testing: young age, multifocal/extraadrenal/malignant disease
If mutation should have annual screening for new or recurrent disease and start genetic testing first degree relatives
Mutations: Von Hippel Lindau, SDH, Men2A/2B
What is the difference in symptoms between adrenal hormone excess and adrenal hormone deficiency?
What is Cushing’s syndrome and what are some causes of this?
Clinical state produced by chronic glucocorticoid excess (raised cortisol)
Causes:
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- Pituitary: adenoma secreting ACTH causing bilateral adrenal hyperplasia
- Adrenal: tumour
- Ectopic ACTH: small cell lung cancer
What are some of the signs and symptoms of Cushing’s disease?
Symptoms: increased weight, mood change, erectile dysfunction, irregular menses, acne
Signs: central obesity, buffalo hymp, moon face, skin thinning, abdominal striae, easy bruising, proximal myopathy
May also have diabetes, osteoporosis and hypertension. 5 year mortality of 50% untreated
What investigations should be done to diagnose Cushing’s disease?
1st Line: (confirm diagnosis with raised plasma cortisol)
- Overnight dexamethasone suppression test
- 24h urinary free cortisol
- Low dose dexamethasone suppression test
2nd Line (localise the source)
- Plasma ACTH
- CRH test
- MRI
What are some causes of pseudocushings? (false +ve dexamethasone suppression test)
- Obesity
- Alcohol excess
- Depression
Once Cushing’s is diagnosed, what tests are done to figure out the cause?
ACTH:
- If low likely to be adrenal cause, do CT adrenals
- If high likely to be ectopic ACTH or pituitary tumour (Cushing’s disease)
CRH
- Inject CRH if ACTH high. In Cushing’s disease will cause a rise in ACTH and cortisol but if ectopic will not
Pituitary MRI
- If suspect pituitary cause
- Can do Inferior Petrosal Sinus Sampling (IPSS) if MRI shows nothing
- If suspect ectopic do whole body CT or PET
How is Cushing’s syndrome managed?
DEPENDS ON CAUSE
- Steroids: stop if possible
- Cushing’s Disease: transphenoidal surgery to remove pituitary adenoma or bilateral adrenalectomy if cannot find source
- Adrenal adenoma/carcinoma: laparoscopic adrenalectomy
- Ectopic ACTH: treat underlying malignancy
- Can give metyrapone and ketoconazole to lower cortisol pre-op or whilst waiting for radiation to take effect
What is hyperparathyroidism and what are some causes of this?
Raised PTH hormone which can cause hypercalcaemia (Ca>2.6)
- Primary Hyperparathyroidism: parathyroid adenoma, hyperplasia of all glands, parathyroid cancer
- Secondary Hyperparathyroidism: anything that causes low Ca (vit D deficiency, chronic renal failure)
- Tertiary Hyperparathyroidism: long term secondary hyperPTH
- Malignant Hyperthyroidism: PTHrP from SCC lung cancers, breast, renal cell carcinoma
What is the presentation of hyperparathyroidism?
- Often asymptomatic and found incidentally on test with raised Ca
- Hypercalcaemia: tiredness, generalised aches, abdominal pains, constipation, polyuria and polydipsia due to nephrogenic DI, renal stones
- Bone resorption due to raised PTH: pain, fractures, osteopenia, Brown Tumours
What investigations should you do to diagnose primary hyperparathyroidism and what will they show?
- Ca: high
- Phosphate: low
- PTH: raised or normal
- ALP: raised due to increased bone turnover
- ECG
- X-rays: decreased bone density (especially distal radius), subperiosteal erosions of phalanges, osteitis fibrosa cystica/brown tumour, salt pepper skull
- Renal US: nephrocalcinosis
How does acute severe hypercalcaemia present and how is it treated?
- May be severely dehydrated and renal impairment. May have short QT, muscle weakness, cognitive disturbance
- Needs urgent treatment to prevent arrhythmias and coma
- IV fluids
- IV bisphosphonates
What is familial hypocalciuric hypercalcaemia?
Autosomal dominant genetic defect in calcium sensing receptor
Distinguish from hyperPTH by low urine calcium/creatinine ratio
Often have family history of mild hypercalcaemia
What is the definition of hypocalcaemia and what are some causes of this?
Symptomatic when Ca<1.9
- Primary hypoparathyroidism
- Post surgical hypoparathyroidism following thyroidectomy
- Vit D deficiency
- Mg deficiency
How does hypocalcaemia present and why is acute severe hypocalcaemia dangerous?
- Muscle cramps
- Carpo-pedal spasm
- Perioral and peripheral paraesthesia
- Chvostek’s and Troussaeu’s sign
Acute severe: laryngospasm, prolonged QT interval, seizures
What is pseudohypoparathyroidism?
Failure of target cell response to PTH so PTH resistance
- Hypocalcaemia
- Hyperphosphataemia
- High PTH
- Normal Vitamin D
What is the typical appearance of someone with pseudohypoparathyroidism?
- Short stature
- Round face
- Short 4th and 5th metacarpals
How are the following causes of hypocalcaemia managed to restore Ca back to normal:
- Acute
- Vit D deficiency
- Hypoparathyroidism
- Mg Deficiency
- Acute: IV calcium gluconate 10mls 10% over 10 mins as life threatening
- Vit D deficiency: Loading dose cholecalciferol 20,000 IU per week for 7 weeks then maintenance of 2000IU a week
- Hypoparathyroidism: Synthetic PTH s/c OR Calcitriol + Sandocal OR Adcal D3
- Mg deficiency: Stop precipitating drugs, IV Mg Sulfate 24mmol/24 hours. If alcohol is the issue or chronic GI loss seek specialist advice
How is acute severe hypercalcaemia managed?
Step 1: IV fluids
Step 2: Once hydrated give bisphosphonates
Step 3: check Ca blood levels daily, bisphosphonates can take 48h
What are some drugs that can lower calcium levels in hypercalcaemia?
- Calcitonin (Miacalcin)
- Bisphosphonates
- Calcimimmetics
- Prednisolone
