Endocrinology and Electrolye Disturbances Flashcards
What is the pathophysiology behind Addisons (primary adrenal insufficiency)?
Destruction of the adrenal cortex leads to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency
What are some of the causes of Addisons ?
- Autoimmunity
- Adrenal metastases (eg from lung, breast, renal cancer)
- Lymphoma
- HIV
What are the causes of secondary adrenal insufficiency?
- Iatrogenic - long-term steroid therapy -> suppression of the pituitary–adrenal axis
What are some of the signs and symptoms of adrenal insufficiency?
- Lean, tanned, tired, tearful ± weakness, anorexia, dizzy, faints, flu-like myalgias/arthralgias.
- Mood: depression, psychosis.
- GI: nausea/vomiting, abdo pain, diarrhoea/constipation, salt craving
- Pigmented palmar creases & buccal mucosa
- Postural hypotension
What tests/ investigations should be performed for suspected Addisons crisis?
- Morning serum cortisol
- Short acth stimulation test (Synacthen® test)
- Plasma cortisol
- Serum ACTH
- ↓Na+ & ↑K+ (due to ↓mineralocorticoid)
- ↓glucose (due to ↓cortisol).
- uraemia, ↑Ca2+, eosinophilia, anaemia.
- Plasma renin/ aldosterone
- CT/MRI
What electrolye changes do you expect to see in Addisons?
- ↓Na+ & ↑K+ ↓glucose (due to ↓cortisol)
- ↑ ACTH
How do you treat Addisons?
- Hydrocortisone: Replace steroids: ~15–25mg daily, 2–3 doses
- Fludrocortisone↓Na+, ↑K+: po from 50–200mcg daily
- Do not abruptly stop steroid use!
How is addisonian crisis managed?
- Bloods: cortisol, ACTH, UE (but treat more urgently than needed)
- Hydrocortisone 100mg IV STAT
- IV fluid bolus for hypotension
- Monitor blood glucose (be aware of hypoglycaemia)
- Continuing treatment
- Glucose IV if hypoglycaemic
- IV fluids
- Hydrocortisone, 100mg/8h IM or IV - change to oral steroids after 72h
- Fludrocortisone - if adrenal disease
What are some of the causes of Cushings syndrome?
ACTH dependent causes
- Cushing’s disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia
- Ectopic ACTH production (5-10%): e.g. SCLC
ACTH independent causes
- iatrogenic: steroids
- adrenal adenoma (5-10%)
- adrenal carcinoma (rare)
- Carney complex: syndrome including cardiac myxoma
- micronodular adrenal dysplasia (very rare)
- Pseudo-Cushing’s
- mimics Cushing’s
- often due to alcohol excess or severe depression
- causes false positive dexamethasone suppression test or 24 hr urinary free cortisol
- insulin stress test may be used to differentiate
What are some of the sx of cushings syndrome?
Round in the middle with thin limbs:
- Round “moon” face
- Central Obesity
- Abdominal striae
- Buffalo Hump (fat pad on upper back)
- Proximal limb muscle wasting
High levels of stress hormone:
- Hypertension
- Cardiac hypertrophy
- Hyperglycaemia (Type 2 Diabetes)
- Depression
- Insomnia
Extra effects:
- Osteoporosis
- Easy bruising and poor skin healing
What are some of the investigations that will be used for Cushings?
Overnight dexamethasone suppression test: patients with Cushing’s syndrome do not have their morning cortisol spike suppressed
24 hr urinary free cortisol
Insulin stress test is used to differentiate between true Cushing’s and pseudo-Cushing’
Other:
- FBC (raised white cells) and electrolytes (potassium may be low if aldosterone is also secreted by an adrenal adenoma)
- MRI brain for pituitary adenoma
- Chest CT for small cell lung cancer
- Abdominal CT for adrenal tumours
How is Cushings Syndrome mxd?
The main treatment is to remove the underlying cause (surgically remove the tumour)
- Cushings disease - Trans-sphenoidal (through the nose) removal of pituitary adenoma
- Surgical removal of adrenal tumour
- Surgical removal of tumour producing ectopic ACTH
Adrenal tumour - laparoscopic adrenalectomy
Medical Mx: metyrapone + ketoconazole
Describe the thyroid HPPA
What basic thyroid function tests are requested for hypo and hyperthyroidism?
- Hyperthyroidism: Ask for T3, t4, and TSH. All will have ↓TSH (except the rare tsh-secreting pituitary adenoma). Most have ↑T4, but ~1% have only raised T3.
- Hypothyroidism suspected or monitoring replacement ℞ T4 and TSH. T3 not very useful. TSH varies through the day (monitor at same time)
- Other
- Thyroid autoantibodies: Anti-TPO: may be increased in autoimmune thyroid disease (Hashimotos or Graves)
- TSH receptor antibody: GRAVE
- USS: for goitre (use FNA to look for cancer)
- Isotope scan: cause of hyperthyroidism
What are some of the sx of thyrotoxicosos/ hyperthyroidism?
Thyroidism
- Tremor
- Heat intolerance/ high HR
- Yawning
- Restlessness
- Oligomennorhoea
- Intolerance to heat
- Diarrhoea
- Irritability/ insomnia
- Sweating
- Muscle wasting
Also: weight loss but increased appetite. Alopecia and urticaria
What are the signs of hyperthyroidism?
- Pulse fast/irregular HR (AF or sinus rhythm)
- HT and flow murmur
- warm moist skin
- fine tremor
- Hyperreflexia
- palmar erythema
- thin hair
- lid lag
- lid retraction (exposure of sclera above iris; causing ‘stare’,
- There may be goitre: thyroid nodules; or bruit depending on the cause
What are the signs unique to Graves’ disease?
- Eye disease: exophthalmos, ophthalmoplegia.
- Pretibial myxoedema: oedematous swellings above lateral malleoli: the term myxoedema is confusing here.
- Skin changes: dermopathy
- Thyroid acropachy: extreme manifestation, with clubbing, painful finger and toe swelling, and periosteal reaction in limb bones.
What tests are used for hyperthyroidism?
- ↓TSH (suppressed), ↑: t4, and t3
- There may be mild normocytic anaemia, mild neutropenia (in Graves’)
- ↑esr, ↑Ca2+, ↑lft.’
- Subclinical
What is Graves and how does it occur?
- Patients are often hyperthyroid but may be, or become, hypo- or euthyroid.
- Cause: circulating igg autoantibodies binding to and activating g-protein-coupled thyrotropin receptors, which cause smooth thyroid enlargement and ↑hormone production
What are the primary and secondary causes of hyperthyroidism?
-
Primary:
- Graves’ disease (younger women)
- Toxic multinodular goitre (older women)
- Solitary toxic adenoma
- Subacute thyroiditis
- Iodine overload
-
Exogenous:
- TSH secreting pituitary tumour
- Others:
- Subacute de Quervain’s thyroiditis
- Drugs: amiodarone, lithium (hypothyroidism more common)
- Postpartum
- TB (rare)
How is hyperthyroidism diagnosed?
- Have a low threshold for doing tfts!
- ↑TSH ↓T4
- In rare secondary hypothyroidism: ↓t4 and ↓tsh or ↔ due to lack from the pituitary
How is hyperthyroidism treated?
Drugs:
- Sx control: β-blockers (eg propranolol 40mg/6h) for sx control
- Anti thyroid meds:
- Titration: carbimazole 20–40mg/24h po for 4wks, reduce according to TFTS every 1–2 months
-
Block-replace: Carbimazole + levothyroxine simultaneously. Use for Graves.
- Carbimazole SE: agranulocytosis (↓↓-neutrophils -> dangerous sepsis): sore throat/mouth ulcers. Must stop and get an urgent FBC if signs of infection
-
Radioiodine (131I): ci: pregnancy, lactation, active hyperthyroidism - risk of thyroid storm.
- Requires lifelong thyroxine replacement
- Thyroidectomy: Risk of damage to recurrent laryngeal nerve (hoarse voice) and hypoparathyroidism (hypocalaemia)
What is thyroiditis?
- Inflammation of the thyroid gland either caused by viral infection, medication (amiodorone) and following childbirth
- Hypothyroid phase follows the initial toxic hyperthyroid phase
What are the complications of hyperthyroidism?
- CVS: HF, Angina, AF
- Osteoporosis
- Ophthalmopathy
- Gynaecomastia.
What are the signs of hypothyroidism?
Tiredness; sleepy, lethargic; ↓mood; cold-disliking; ↑weight; constipation; menorrhagia; hoarse voice; ↓memory/cognition; dementia; myalgia; cramps; weakness.
What are the signs of hypothyroidism?
- bradycardic
- reflexes relax slowly
- ataxia (cerebellar)
- dry thin hair/skin
- yawning/drowsy/coma
- cold hands
- ascites ± non-pitting oedema (lids; hands; feet) ± peri-cardial or pleural effusion
- round puffy face/double chin/obese
- defeated demeanour
- immobile ± ileus; ccf
- Also: neuropathy; myopathy; goitre
What are some of the causes of hypothyroidism? What are some that are seen in kids?
-
Causes of primary autoimmune hypothyroidism:
- Primary atrophic hypothyroidism,
- Autoimmune: Hashimotos
- Iatrogenic: Post-thyroidectomy + radioiodine treatment
- Pregnancy
- Drugs: Antithyroid drugs, amiodarone, lithium, iodine.
-
Children:
- Neonatal hypothyroidism caused by iodine deficiency -> cretinism + mental retardation
- Familial thyroid dyshormogenesis
- Secondary: Not enough tsh v. rare
How is hypothyroidism managed?
-
Healthy and young:
-
Levothyroxine (t4), 50–100ug/24h po; review at 12wks. Adjust 6-weekly by clinical state and to normalize but not suppress TSH (keep tsh >0.5mu/L). Wait ~4wks before checking TSH to see if a dose change is right.
- If T4 raised, but TSH still high: poor complicance
- If T4 raised but TSH too low: over replacment
-
Levothyroxine (t4), 50–100ug/24h po; review at 12wks. Adjust 6-weekly by clinical state and to normalize but not suppress TSH (keep tsh >0.5mu/L). Wait ~4wks before checking TSH to see if a dose change is right.
- Elderly or ischaemic heart disease:
- Levothyroxine: 25ug/24h; ↑dose by 25mcg/4wks according to TSH
- Discontinue amiodorone: Thyroidectomy may be needed if amiodarone cannot be discontinued
- if managing 2ndary hypo: T4 should be replaced to upper part of normal limit
- If pt remains symptomatic despite normal thyroid function investigate other pathology
What is subclinical hypothyroidism?
Normal T4 but elevated TSH
Think of it as assymptomatic hypothyroidism
How do you manage subclinical hypothyroidism?
- Assymptomatic - treatment may not be needed - thyroid function can revert back to normal - repeat testing
- Treat if:
- If TSH > 10U/L - start thyroxine even if assymptomatic - high likelihood of progressing to frank hypothyroidism
- If pregnant: TSH 5-10miU/L - start thyroxine
- If +ve for thyroid antibodies - annual thyroid function test
What thyroid results would be expected for different hyper/ hypo conditions, thyroiditis etc?
Subclinical hyperthyroidism - Suppressed TSH/ normal T3 + T4
How does PTH hormone work?
- ↑osteoclast activity releasing Ca2+ and PO43− from bones
- ↑Ca2+ and ↓PO43− reabsorption in the kidney
- active 1,25dihydroxy-vitamin d3 production is ↑. Overall effect is ↑Ca2+ and ↓PO43−.
How do you get hyperparathyroidism?
- Primary: solitary adenoma, hyperplasia of all glands, parathyroid cancer.
- Secondary: ↓Ca2+, ↑pth (appropriately)
What are the signs of hypercalcaemia?
‘Bones, stones, groans, and psychic moans.’
- Abdominal pain
- Vomiting
- Constipation
- Polyuria; polydipsia
- Depression
- Anorexia
- Weight loss
- Tiredness
- Weakness
- Hypertension
- Confusion
- Pyrexia
- Renal stones; renal failure
What ECG changes are seen of hypercalcaemia?
↓qt interval.
What are the causes of hypercalcaemia?
- Most common: malignancy (eg from bone metastases: breast, kidney, lung, thyroid, prostate, ovary, colon, myeloma, PTHrP)
- Primary hyperparathyroidism.
- Others: sarcoidosis, vit D intoxication, thyrotoxicosis, lithium, tertiary hyperparathyroidism, milk-alkali syndrome, and familial benign hypocalciuric hypercalcaemia
Which cancers secrete PTHrP?
- Breast carcinoma
- Renal cell cancer
- Small cell lung cancer
What investigations are used for hypercalcaemia and what do we expect them to show?
- The main distinction is malignancy vs 1° hyperparathyroidism.
- Malignancy: ↓albumin, ↓Cl−, alkalosis, ↓K+, ↑PO43−, ↑alp.
- Hyperparathyroidism: ↑PTH
- Other investigations: FBC, protein electrophoresis, cxr, isotope bone scan, 24h urinary Ca2+ excretion (for familial hypocalciuric hypercalcaemia).
How is hypercalcemia treated acutely?
- Dehydrated? Give iv 0.9% saline
-
Bisphosphonates: These prevent bone resorption by inhibiting osteoclast activity.
- Pamidronate: single dose. Infuse slowly, eg 30mg in 300mL 0.9% saline over 3h via a largish vein. Max dose 90mg
- Zoledronic acid: more effective in reducing serum Ca2+. Single dose 4mg iv (diluted to 100mL, over 15min) across 1 wk.
- Demusomab
- Chemotherapy: malignancy.
- Steroids: sarcoidosis, eg prednisolone 40–60mg/d.
- Salmon calcitonin: now rarely used.
How is hypercalcemia treated more long term?
- Cinacalcet - increased sensitivity of PT cells to calcium -> reducing PTH secretion and reversing hyperparathyroidism + hypercalcaemia secondary to that
- Calcitonin
- Desunomab - calcium lowering therapy with reabsorptive agents
- Avoid medications that worsen hypercalcaemia : e.g., thiazide diuretics, calcitriol [(1,25-dihydroxyvitamin D)], calcium supplementation, antacids, lithium
What are the sx and signs of hypocalcaemia?
SPASMODIC
- Spasms (carpopedal spasms = Trousseau’s sign)
- Perioral paraesthesiae
- Anxious, irritable, irrational
- Seizures
- Muscle tone ↑ in smooth muscle—hence colic, wheeze, and dysphagia
- Orientation impaired (time, place, and person) and confusion
- Dermatitis (eg atopic/exfoliative)
- Impetigo herpetiformis (↓Ca2+ and pustules in pregnancy—rare and serious)
- Chvostek’s sign; choreoathetosis; cataract; ccardiomyopathy (long qt interval on ecg).
What are some of the causes of hypocalcaemia?
What ECG changes are seen with hyperkalaemia?
- Tall tented T waves
- Absent/ flattened P waves
- Slurred ST segment - sine wave
- Prolonged QRS
- 3Bs: bradycardia, block, bizarre
