Describe Graves disease
Hyperthyroidism due to pathological stimulation of TSH receptor
Autoimmune induced excess production of TH
Clinical presentation of Graves disease
Rapid Heart beat
Tremor
Diffuse palpable goiter with audible bruit
Eye problems: bulging outwards and lid retraction
Graves’ opthalmopathy
Graves dermopathy (rare)
Thyroid acropachy (clubbing, finger and toe swelling)
Pathophysiology of Graves disease
TSH receptor stimulating antibodies (TSHR-Ab) recognise and bind to the TSH receptors in thyroid
- > stimulates thyroid hormone production T4 and T3
- > thyroxine (T4) receptors in the pituitary gland are activated by excess hormone
- > reduced release of TSH in a negative feedback look
- > Very high levels of circulating thyroid hormones, with a low TSH
- > as well as excess secretion of thyroid hormones, also results in hyperplasia of thyroid follicular cells resulting in hyperthyroidism and diffuse goitre
Aetiology/Risk factors of Graves disease
Some genetic element - association with HLA-B8, DR3 & DR2.
Smoking
Stress
High iodine intake
E.coli and other gram-NEGATIVE organisms contain TSH-binding sites so may initiate pathogenesis via ‘molecular mimicry’
Autoimmune disease.
Associated with other autoimmune diseases, such as Vitiligo (pale patches on skin), Addison’s, type 1 DM, pernicious anaemia and myasthenia gravis.
Epidemiology of Graves disease
Most common cause of hyperthyroidism (2/3 of cases)
More common in females
Typically presents at 40-60 years (appear earlier if maternal family history)
Diagnostic of Graves disease
High T3 and T4
Lower TSH than normal
Mild neutropenia
*TSH receptor stimulating antibodies (TSHR-Ab) raised
Treatment of Graves disease
Antithyroid drugs (Carbimazole or Propylthiouracil) with either dose titration or ‘block and replace’.
Thyroidectomy.
Radioactive iodine.
Beta blockers
Complications of Graves disease
Thyroid storm: treat with Propylthiouracil
Also similar to auto-antigen, can result in retro-orbital inflammation - graves opthalmopathy
Describe Hashimotos thyroiditis
Hypothyroidism due to aggressive destruction of thyroid cells
(autoimmune hypothyroidism)
Clinical Presentation of Hashimotos thyroiditis
Thyroid gland may enlarge rapidly, occasionally with dyspnoea or dysphagia from pressure on the neck
Hypothyroidism: Fatigue, cold intolerance, slowed movement, decreased sweating
Pathophysiology of Hashimotos thyroiditis
Aggressive destruction of thyroid cells by various cell and antibody mediated immune processes.
Antibodies bind and block TSH receptors -> inadequate thyroid hormone production and secretion.
Thyroid peroxidase is essential hormone for production and storage of thyroid hormone: Thyroid peroxidase antibodies (TPO-Ab) are present in high titres
Aetiology of Hashimotos thyroiditis
What are triggers?
Unknown.
Autoimmune.
Some genetic element.
Triggers; iodine, infection, smoking and possibly stress
Epidemiology of Hashimotos thyroiditis
12-20 times more frequent in women.
Most common cause of goitrous hypothyroidism.
Diagnostic tests of Hashimotos thyroiditis
TSH levels, usually raised in hypothyroidism.
Thyroid antibodies.
Treatment of Hashimotos thyroiditis
Levothyroxine therapy (may shrink the goitre) Thyroid hormone replacement Resection of obstructive goitre.
Complications of Hashimotos thyroiditis
Hyperlipidemia
Define Sequelae
condition which is the consequence of a previous disease or injury
Sequelae of Hashimotos Thyroiditis
Hashimotos encephalopathy
Describe hypothyroidism
Reduced action/levels of thyroid hormone
Types of hypothyroidism (briefly explain each)
Primary - disease associated with thyroid
Secondary - disease associated with pituitary or hypothalamus
Transient - disease associated with treatment withdrawal
Clinical presentation of Hypothyroidism
(same for all 3 types)
Insidious onset.
Tiredness, lethargy, intolerance of cold, goitre, slowing of intellectual activity, constipation, deep hoarse voice.
Puffy face, hands and feet.
Menorrhagia, weight gain, myalgia, dementia, myxoedema (accumulation of mucopolysaccharide in SC tissue)
Pathophysiology of Primary Hypothyroidism
Aggressive destruction of thyroid cells by various cell and antibody mediated immune processes.
Antibodies bind and block TSH receptors
-> inadequate thyroid hormone production and secretion
Pathophysiology of Secondary Hypothyroidism
Reduced release or production of TSH by pituitary or hypothalamus (respectively)
-> reduced T3 and T4 release
Pathophysiology of Transient Hypothyroidism
The thyroid overcompensates until it can reestablish correct concentrations of Thyroid hormone
Aetiology of Primary Hypothyroidism
Autoimmune hypothyroidism (Hashimoto’s), iodine deficiency, congenital defects
Aetiology of Secondary Hypothyroidism
Isolated TSH deficiency, hypopituitarism (due to neoplasm, infection), hypothalamic disorders (neoplasms, trauma)
Aetiology of Transient Hypothyroidism
Withdrawal of thyroid suppressive therapy such as radioactive iodine
Epidemiology of Primary Hypothyroidism
More common in Japan
Diagnostic tests of Hypothyroidism
Thyroid Function Tests (TFTs)
Serum free T4 levels low
Thyroid antibodies may be present
Blood tests:
Raised serum aspartate transferase levels from muscle and/or liver
Increase serum creatinine kinase levels associated with myopathy
Hypercholesterolaemia
Hyponatraemia due to an increase in ADH and impaired free water clearance
Treatment of Primary Hypothyroidism
Thyroid hormone replacement (Levothyroxine) - dose is titrated until TSH normalises
Resection of obstructive goitre
Treatment of Secondary Hypothyroidism
Thyroid hormone replacement (Levothyroxine). Treat underlying cause
Treatment of Transient Hypothyroidism
Remits on its own
Complications of Hypothyroidism
Myxoedema coma (20-50% mortality) Reduced level of consciousness, seizures, cardiac failure, hypothermia and hypothyroidism
severe hypothyroidism/reduced T4
Types of thyroid cancer/malignancies
Papillary (named for papillae among its cells on microscopy)
Follicular
Anaplastic (one of most aggressive cancers in human)
Lymphoma
Medullary
What types of thyroid cancers fit this clinical presentation:
Usually asymptomatic thyroid nodule (usually hard and fixed). Possibly enlarged lymph nodes on examination.
Papillary
Follicular
Anaplastic
Clinical presentation of Lymphoma (thyroid malignancy)
Rapidly growing mass in the neck
Clinical presentation of Medullary cancer (thyroid malignancy)
Diarrhoea
Flushing episodes (similar to Carcinoid syndrome)
Itching
Pathophysiology of papillary thyroid cancer
Tends to spread locally in neck, compressing the trachea
Pathophysiology of follicular thyroid cancer
May infiltrate neck, but greater propensity to metastasise to lung and bones relative to papillary
Pathophysiology of anaplastic thyroid cancer
Follicular cells of the thyroid, but does not retain original cell features like iodine uptake or synthesis of thyroglobulin
Pathophysiology of lymphoma thyroid cancer
Almost always non-hodgkins lymphoma
Pathophysiology of medullary thyroid cancer
Parafollicular calcitonin-producing C cells. Produce large amounts of peptide such as calcitonin
Aetiology of medullary thyroid cancer
Often familial
Epidemiology of papillary thyroid cancer
70% of thyroid cancer.
Young people.
Three times more common in women.
Epidemiology of follicular thyroid cancer
20% of thyroid cancer.
Middle age.
Tends to be in areas of low iodine.
Epidemiology of anaplastic thyroid cancer
<5% of thyroid cancer
Epidemiology of lymphoma thyroid cancer
2% of thyroid cancer.
Often associated with Hashimoto’s thyroiditis.
Epidemiology of medullary thyroid cancer
5% of thyroid cancer.
More sporadic than hereditary.
Diagnostic tests of thyroid cancer
Fine needle aspiration.
Differences: Medullary; elevated serum calcitonin.
Treatment of medullary thyroid cancer
Total thyroidectomy and prophylactic central lymph node dissection
Which thyroid cancers would you treat via:
External radiotherapy to provide relief (largely palliative)
Anaplastic
Lymphoma
Treatment of Papillary thyroid cancer
Total thyroidectomy -> ablative radioactive iodine
same for follicular thyroid cancer
Treatment of Follicular thyroid cancer
Total thyroidectomy -> ablative radioactive iodine
same for papillary thyroid cancer
Describe Cushing’s syndrome
Persistently and inappropriately elevated circulating glucocorticoid (cortisol)
This is attributed to inappropriate ACTH secretion from the pituitary (due to tumour)
Clinical presentation of Cushing’s syndrome
(truncal) Obesity (fat distribution central, buffalo hump)
plethoric complexion
Rounded ‘moon face’, thin skin, bruising, striae, hypertension, pathological fractures
Acne
Cataracts, Ulcers, Skin striae, Hyperglycarmia/hypertension, Increased infection, Necrosis, Glucosuria/gonal dysfunction
Pathophysiology of Cushing’s syndrome
Excess cortisol can either result from excess ACTH which in turn stimulates excess cortisol release or from neoplasms in the adrenals which in turn stimulate the zona reticularis to release more cortisol.
Excess can also result from ingesting excess glucocorticoid itself e.g. PREDNISOLONE
Many features due to protein-catabolic effects of cortisol; thin skin, easy bruising, striae. Excessive alcohol consumption can mimic the clinical and biochemical signs (Pseudo-Cushings’s), but resolves on alcohol recession
Aetiology of Cushing’s syndrome
ACTH (adrenocortiotropic hormone) dependent disease:
Cushings disease - Bilateral adrenal hyperplasia from an ACTH-secreting pituitary adenoma (benign).
Ectopic Cushings syndrome - paraneoplastic syndrome (tumour elsewhere in body producing ACTH - especially small cell lung cancer and carcinoid tumours)
ACTH treatment e.g. for asthma
ACTH independent:
Excess oral steroids! (iatrogenic)
Adrenal adenomas,
adrenal carcinomas, excess glucocorticoid administration (most common) e.g. Prednisolone
Epidemiology of Cushing’s syndrome
10/1,000,000.
Higher incidence in diabetes.
2/3 cases are Cushing’s disease.
Most common cause is oral steroids i.e. glucocorticoid therapy.
Spontaneous endogenous causes are rare, but 80% due to raised ACTH, with pituitary adenoma being the most common cause
Diagnostic tests of Cushing’s syndrome
Confirm raised cortisol: 48 hour low-dose dexamethasone: Fail to suppress cortisol is diagnostic of Cushings.
Urinary free cortisol over 24hrs (normal levels mean Cushings unlikely).
Late night salivary cortisol. Establishing cause: CT and MRI of renal and pituitary
NOT random plasma cortisol test as cortisol levels change through day (stress, illness, morning)
Treatment of Cushing’s syndrome
Stop steroids if iatrogenic
Transphenoidal removal of pituitary adenoma if Cushings disease
Adrenalectomy or Radiotherapy if Adrenal Adenoma
Ectopic ACTH: Surgical removal of tumour if location known
Cortisol synthesis inhibition: metyrapone, ketoconazole
Complications of Cushing’s syndrome
Hypertension, obesity, death
Describe Acromegaly
Overgrowth of all organ systems due to excess GH
Increased production of growth hormone occurring in adults after fusion of the epiphyseal plates
Clinical Presentation of Acromegaly
Slow onset (old photos). Larger hands/feet. Large tongue, prognathism, interdental separation, spade-like hands.
If (acromegaly) tumour arises before fusion of epiphyseal plates (children bones), what condition can result instead/like acromegaly
Gigantism
worse as don’t stop growing as bones not developed
Pathophysiology of Acromegaly
GH acts directly on tissues such as liver, muscle bone or fat, as well as indirectly through induction of insulin like growth factor. Excess causes uncontrolled growth of organ systems.
Very slow insidious onset over many years
Aetiology of Acromegaly
Usually excessive GH secretion by a pituitary tumour. Other GH releasing tumours possible (hypothalamus, specific lung cancers).
Mainly pituitary adenoma
Epidemiology of Acromegaly
3 per million per year
Average 40 yrs.
Same in male and females
Diagnostic tests of Acromegaly
Glucose tolerance test: IGF-1 raised. GH raised.
MRI the pituitary fossa for adenomas
Treatment of Acromegaly
Transsphenoidal resection surgery. Dopamine agonists (cabergoline), somatostatin analogues (octreotide) and GH receptor antagonists (pegvisomant)
Complications of Acromegaly
Hypertension, diabetes.
Untreated adenoma can impact the optic chiasm -> blindness
Colorectal cancer
Describe Conn’s syndrome
Primary hyperaldosteronism
High aldosterone levels independent of Renin-Angiotensin system
Clinical presentation of Conn’s syndrome
Hypertension (possibly low urine output) Hypokalemic: -Constipation -Weakness and cramps -Paraesthesia -Polyuria and polydipsia
What is secondary hyperaldosteronism
Hyperaldosteronism due to high renin levels
What is another name for Primary Hyperaldosteronism
Conn’s syndrome
Pathophysiology of Conn’s syndrome
Aldosterone causes an exchange of transport of sodium and potassium in the distal renal tubule.
Therefore, hyperaldosteronism causes increased reabsorption of sodium (and water) and excretion of potassium
Aetiology of Conn’s syndrome
Adrenal adenoma secreting aldosterone in Conn’s syndrome (or possibly bilateral adrenal hyperplasia)
Diagnostic tests of Conn’s syndrome
Plasma Aldosterone (increased) and Renin (decreased)
U and E
Adrenal CT
ECG
Treatment of Conn’s syndrome
Adenoma: Surgical removal (laparoscopic adrenalectomy)
Hyperplasia: aldosterone antagonist or potassium-sparing diuretic (spironolactone)
Describe Adrenal Insufficiency
Hypoadrenalism
due to destruction or reduced stimulation of adrenal cortex
What are types of Adrenal Insufficiency and describe the difference between the two
Primary insufficiency - Destruction of adrenal cortex
Secondary insufficiency - Reduction of adrenal cortex stimulation
What is another name for Primary Adrenal Insufficiency
Addison’s disease
What is key difference in clinical presentation between Primary and Secondary adrenal insufficiency
Primary - Hyperpigmentation
Secondary - no pigmentation
*Why does Primary Adrenal Insufficiency result in hyper pigmentation but Secondary AI does not?
Primary:
Destruction of adrenal cortex -> Less cortical products. Excess ACTH -> stimulates melanocytes -> hyper pigmentation
Secondary:
Reduction of adrenal cortex stimulation -> Less cortical products. Low ACTH -> less melanocytes stimulation -> no pigmentation
Clinical presentation of Addison’s disease (primary adrenal insufficiency)
Thin, tanned, tired and tearful.
HYPER-pigmentation.
Insidious. Non-specific symptoms; lethargy, depression, anorexia, weight loss, weakness and fatigue. Postural hypotension. GI: N+V, abdominal pain
Clinical presentation of Secondary Adrenal Insufficiency
Insidious. Non-specific symptoms; lethargy, depression, anorexia, weight loss, weakness and fatigue. Postural hypotension. Thin, tanned, tired and tearful.
NO pigmentation
Pathophysiology of Addison’s disease (primary adrenal insufficiency)
Autoimmune destruction of the entirety adrenal cortex. Associated with other autoimmune conditions.
Loss of cortex -> reduction in ability to produce Cortisol and/or Aldosterone.
Excess ACTH stimulates melanocytes -> pigmentation.
Pathophysiology of Secondary Adrenal Insufficiency
Inadequate pituitary or hypothalamic stimulation of the adrenal glands. No pigmentation, since ACTH levels are low.
Aetiology of Addison’s disease (primary adrenal insufficiency)
Organ specific autoantibodies in 90% of cases. Rarely; adrenal gland tuberculosis, surgical removal or haemorrhage
Addisons is commonest cause in the UK of adrenal insufficiency, TB is most common cause WORLDWIDE
Aetiology of Secondary Adrenal Insufficiency
Hypothalamic-pituitary disease or from long term steroid therapy leading to hypothalamic-pituitary-adrenal suppression.
Iatrogenic
Epidemiology of Addison’s disease (primary adrenal insufficiency)
1/10,000
Addisons is commonest cause in the UK of adrenal insufficiency, TB is most common cause WORLDWIDE
Epidemiology of Secondary Adrenal Insufficiency
200/1,000,000
Diagnostic tests of Addison’s disease (primary adrenal insufficiency)
Sodium reduction, potassium elevation due to low aldosterone.
Short ACTH stimulation test (Give ACTH (synacthen), then measure cortisol level; in Addison, cortisol remains low after giving ACTH).
test for 21-hydroxylase adrenal autoabs (+ve in 80% Addisons)
Diagnostic tests of Secondary Adrenal Insufficiency
Long ACTH test (synacthen test) to distinguish from primary: ACTH raised in primary, lowered in secondary
Treatment of Addison’s disease (primary adrenal insufficiency)
Cortisol hormone replacement - glucocorticoid (hydrocotisone)
Aldosterone replacement via mineralocorticoid (fludrocortisone) - this also helps treat postural hypotension
Treatment of Secondary Adrenal Insufficiency
Hormone replacement (just hydrocortisone). If from steroid therapy; remove steroids very slowly
Complications of Addison’s
Adrenal crisis (patients present with shock, severe hypotension, lost a lot of fluid via vomitting and reduced reabsorption of Na+ -> treat with fluid, hydrocortisone) Reduced QOL
Describe Adrenal Hyperplasia
Defective enzymes mediating the production of adrenal cortex products.
Low cortisol, maybe low aldosterone, high androgen
Clinical presentation of Adrenal Hyperplasia
In severe forms; salt loss. Female: Ambiguous genitalia with common urogenital sinus. Male: no signs at birth, bar subtle hyperpigmentation and possible penile enlargement.
Pathophysiology of Adrenal Hyperplasia
Defective 21-hydroxylase -> disruption of cortisol biosynthesis. This causes cortisol deficiency, with or without aldosterone deficiency and androgen excess. In severe forms, aldosterone deficiency -> salt loss
Aetiology of Adrenal Hyperplasia
Genetic 21-hydroxylase deficiency is the cause of about 95% of cases.
Diagnostic tests of Adrenal Hyperplasia
Serum 17-hydroxyprogesterone (precursor to cortisol) levels: high
Treatment of Adrenal Hyperplasia
Glucocorticoids: Hydrocortisone
Mineralocorticoids: Control electrolytes
If salt loss: Sodium chloride supplement
Describe Diabetes Insipidus
Hyposecretion or insensitivity to ADH
Types of Diabetes Insipidus and their difference
Cranial - Hyposecretion
Nephrogenic - Insensitivity
Clinical presentation of Diabetes Insipidus
Polyuria
Compensatory polydipsia
Dehydration
Pathophysiology of Cranial Diabetes Insipidus
Disease of the hypothalamus, where ADH is produced -> Insufficient ADH production. Interestingly, damage to the Posterior Pituitary gland, does not lead to ADH deficiency, as it can still ‘leak’ out.
Pathophysiology of Nephrogenic Diabetes Insipidus
Depends on the aetiology. Can be due to disruption of the channels, damage to the kidney -> *Lack of response to ADH
Aetiology of Cranial Diabetes Insipidus
trauma, pituitary tumour
Neurosurgery,, infiltrative disease, idiopathic Genetic: Mutations in the ADH gene
Aetiology of Nephrogenic Diabetes Insipidus
Hypokalaemia, hypercalcaemia, drugs, renal tubular acidosis, sickle cell, prolonged polyuria, chronic kidney disease Genetic: Mutation in ADH receptor
Epidemiology of Diabetes Insipidus
1/25,000
Diagnostic tests of Diabetes Insipidus
Water deprivation test: Confirm DI
Restrict fluid, measure osmolarity (urine osmolarity low means DI)
Desmospressin (ADH analogues) to differentiate between cranial and nephrogenic
Urine volume: Confirm polyuria.
U&Es (urine and electrolytes): Confirm not a more common cause of polyuria
MRI of hypothalamus: Confirm CDI
Treatment of Cranial Diabetes Insipidus
Desmopressin.
Mild cases: thiazide diuretics, carbamazepine and chlorpropramide to sensitise the renal tubules to endogenous vasopressin.
Treatment of Nephrogenic Diabetes Insipidus
Bendroflumethizide (diuretics) -> cause more Na+ excretion
NSAIDs - reduce GFR
Treatment of the cause.
Describe syndrome of inappropriate ADH secretion
Continued ADH secretion in spite of plasma hypotonicity and normal plasma volume
(opposite of DI)
Clinical presentation of syndrome of inappropriate ADH secretion
Nausea, anorexia, confusion
Concentrated urine
Irritability and headache with mild dilutional hyponatraemia.
Fits and coma with severe hyponatraemia.
Pathophysiology of syndrome of inappropriate ADH secretion
Ectopic (abnormal) production increases the amount of ADH produced, beyond mechanisms of control.
Aetiology of syndrome of inappropriate ADH secretion
Disordered hypothalamic-pituitary secretion, or ectopic production of ADH.
Neurological: Tumour, trauma, infection
Pulmonary: Lung small cell cancer (common), mesothelioma, cystic fibrosis
Drugs an CNS disorders also
Diagnostic tests of syndrome of inappropriate ADH secretion
(FBC)
Measure urine and plasma osmolarity
Treatment of syndrome of inappropriate ADH secretion
Route: IV
Treat underlying cause
Restrict fluid
Vasopressin receptor antagonists (vaptans)
Describe Hyperparathyroidism
Excessive secretion of PTH
Types of hyperparathyroidism (describe each briefly)
Primary - One parathyroid gland produces excess PTH
Secondary - Increased secretion of PTH to compensate hypocalcemia
Tertiary - Autonomous secretion of PTH due to CKD (chronic kidney disease)
Clinical presentation of primary hyperparathyroidism
70-80% asymptomatic. Bone pain, renal calculi, nausea, neuropsychiatric (Bones, stones, abdominal groans and psychic moans)
Bone resorption causes pain, fracture, osteoporosis. Leads to hypercalcaemia (weak, tired, depressed, thirsty, renal stones)
Hypertension
Clinical presentation of secondary hyperparathyroidism
Kidney disease, with skeletal or cardiovascular complications
Clinical presentation of tertiary hyperparathyroidism
Bone pain, renal calculi, nausea, neuropsychiatric (Bones, stones, abdominal groans and psychic moans)
Pathophysiology of primary hyperparathyroidism
Adenoma or hyperplasia provides additional secretive tissue to provide excess PTH
Pathophysiology of secondary hyperparathyroidism
Parathyroid gland becomes hyperplastic in response to chronic hypocalcemia
Pathophysiology of tertiary hyperparathyroidism
Glands become autonomous, producing excess of PTH even after the correction of calcium deficiency
Aetiology of primary hyperparathyroidism
Single parathyroid adenoma or hyperplasia
80% = solitary adenoma
20% = parathyroid hyperplasia
(parathyroid cancer rare)
Aetiology of secondary hyperparathyroidism
CKD (any condition with hypocalcaemia, such as vitamin D deficiency, GI disease such as Crohn’s preventing absorption of calcium)
Aetiology of tertiary hyperparathyroidism
Develops from secondary hyperparathyroidism
Epidemiology of primary hyperparathyroidism
Third most common endocrine disorder
Diagnostic tests of primary hyperparathyroidism
Bloods: Hypercalcaemia
↑PTH, ↑Ca, ↓Phosphate
Increased 24hour urinary calcium excretion
DEXA bone scan for osteoporosis
Diagnostic tests of secondary hyperparathyroidism
Bloods: low serum calcium
↑PTH, ↓Ca, ↑Phosphate
DEXA bone scan for osteoporosis
Diagnostic tests of tertiary hyperparathyroidism
Bloods: Raised calcium, raised PTH
↑PTH, ↑Ca, ↑Phosphate
Increased 24hr urinary calcium excretion
Treatment of primary hyperparathyroidism
Surgical removal of adenoma (treat underlying cause).
Fluids and bisphosphonates.
Treatment of secondary hyperparathyroidism
Calcium correction. Treat underlying condition
Treatment of tertiary hyperparathyroidism
Calcium mimetic (Cinacalcet), total or subtotal parathyroidectomy
Complications of primary hyperparathyroidism
Hypercalcemia
Complications of secondary hyperparathyroidism
Development into tertiary hyperparathyroidism
Complications of tertiary hyperparathyroidism
Transient hypocalcaemia follows parathyroidectomy
Describe hypoparathyroidism
Low levels of PTH
Also:
Hypocalcemia and Hyperphosphataemia
Clinical Presentation of hypoparathyroidism
Increased excitability of muscles and nerves.
Numbness around the mouth/extremities, cramps, tetany, convulsions.
Chvostek and Trousseau signs.
Pathophysiology of hypoparathyroidism
PTH stimulates the activation of vitamin D, which facilitates intestinal calcium absorption, renal reabsorption of calcium as well as calcium release from bone. Phosphate reabsorption is inhibited by PTH. In disease, these processes do not occur.
Aetiology of hypoparathyroidism
May be transient.
Most commonly follows anterior neck surgery (secondary).
VD and/or Magnesium deficiency (Mg used in PTH production)
Genetic: Can be due to defects in PTH gene.
Can be autoimmune destruction of PT glands.
Epidemiology of hypoparathyroidism
Rare
Diagnostic tests of hypoparathyroidism
Bloods: Calcium and PTH low, phosphate high
Signs and symptoms of hypocalcaemia
Treatment of hypoparathyroidism
Acute: IV calcium
Persistent: Vitamin D analogue (alfacalcidol)
Calcitriol (prevent low calcium levels)
Synthetic PTH
Complications of hypoparathyroidism
Over-treatment with vitamin D -> hypercalcaemia
Clinical Presentation of Hypercalcaemia
Can be asymptomatic.
More severe: malaise, bone pain, abdominal pain, nausea, constipation, psychiatric moans (affects NS - lethargy, fatigue, memory loss, depression)
Occasionally renal calculi and CKD.
Polyuria and polydipsia
On PQRST of an ECG, what interval is affected by hypercalcaemia and what is the change
Shortening of QT interval
ventricular depolarisation (QRS) and re-polarisation (T)
Pathophysiology of Hypercalcaemia
Ectopic secretion of PTH is very rare. Tumour related hypercalcaemia tends to work by a secretion of a peptide with PTH-like activity, direct invasion of bone and production of local factors for calcium mobilisation.
Aetiology of Hypercalcaemia
> 90% of cases; primary hyperparathyroidism and malignancy. Primary hyperparathyroidism is caused by a single parathyroid gland adenoma, occasionally hyperplasia
Epidemiology of Hypercalcaemia
30/100,000
Diagnostic tests of Hypercalcaemia
Bloods: Raised calcium
CXR
Malignancy: raised calcium and phosphate in blood
ECG: tented T and short QT interval
Treatment of Hypercalcaemia
Give saline drip (NaCl) which will help to dilute the levels of calcium in the blood if you bring the overall body fluids up (or can give Loop diuretic to return calcium to normal)
Bisphosphonate - encourage osteoclasts to undergo apoptosis so there is less bone breakdown
Primary hyperparathyroidism: surgical removal
Clinical presentation of Hypocalcemia
Increased excitability of muscles and nerves. Numbness around the mouth/extremities, cramps, tetany, convulsions. Chvostek and Trousseau signs.
On PQRST of an ECG, what interval is affected by hypocalcaemia and what is the change
QT prolongation (primarily by prolonging the ST segment/interval between depolarisation and repolarisation)
Pathophysiology of Hypocalcemia
CKD -> Increased phosphate -> Microprecipitation of calcium phosphate in tissues -> Low serum level of calcium.
CKD -> Inadequate production of active vitamin D.
Aetiology of Hypocalcemia
Increased serum phosphate:
Chronic kidney disease (most common) - poor calcium uptake, Phosphate therapy, Hypoparathyroidism (decreased phosphate excretion)
(Reduced PTH function: Post thyroidectomy and parathyroidectomy)
Low Phosphate:
Osteomalacia - soft bones due to low calcium and vitamin D deficiency, Acute pancreatitis, Vitamin D deficiency (reduced exposure to sunlight) - poor Ca uptake in GI tract and decreased kidney reabsorption
Diagnostic tests of Hypocalcemia
History. eGFR to search for CKD. PTH, Vitamin D.
Treatment of Hypocalcemia
Acute: IV calcium
Persistent: In vitamin D deficiency, vitamin D supplement. OR Calcium gluconate
(If hypoparathyroidism; alfacalcidol)
Mild - ADCAL
Complication of Hypocalcemia
death possible
Clinical presentation of Hyperkalemia
Few symptoms until it can cause MI.
Impaired neuromuscular transmission (muscle weakness and paralysis)
On PQRST of an ECG, what interval is affected by hyperkalemia and what is the change
Tall tented T waves
Pathophysiology of Hyperkalemia
Renal impairment can lead to retention of potassium in the nephron.
This is possible with potassium sparing diuretic.
Excessive K consumption at a fast rate -IV fluids
Aetiology of Hyperkalemia
Renal impairment (most common) and drug interference with potassium excretion. Elevated without either of these may be artifactual.
Diagnostic tests of hyperkalemia
Bloods: Check potassium. Recheck unexpected result.
ECG: tall tented T waves, (prolonged PR), widened QRS and reduced P
QRS>0.12s
Treatment of hyperkalemia
Dietary potassium restriction and loop diuretic.
Non urgent - Polystyrene sulphonate resin= Binds K+ in the gut decreasing uptake
Urgent - Calcium gluconate= decreases VF risk in the heart
Insulin= drives K+ into the cells
Complication of hyperkalemia
Myocardial infarction -> Death
Clinical presentation of Hypokalemia
Usually asymptomatic, possibly muscle weakness. Increased risk of cardiac arrhythmias. Polyuria.
On PQRST of an ECG, what interval is affected by hypokalemia and what is the change
T wave inversion
possible prominent U wave
Pathophysiology of hypokalemia
and how it leads to decreased mysocyte excitability
Excessive loss of potassium through the kidneys in response to aldosterone or diuretic therapy.
GI fluid loss -> less chloride -> increase in aldosterone -> Decreased potassium reabsorption
Low K+ in the serum (ECF) causes a water concentration gradient out of the cell (ICF)
Increased leakage from the ICF causing hyperpolarisation of the myocyte membrane decreasing myocyte excitability.
Aetiology of hypokalemia
Diuretic treatment and hyperaldosteronism.
Possibly due to loss of GI fluids by constant vomiting/diarrhoea.
Fasting and anorexia
Diagnostic tests of hypokalemia
Bloods: low magnesium and potassium
ECG: Flat T waves, ST depression, Long PR and prominent U waves
(U have no Pot (K+) & no Tea but a Long PR & a long QT. )
[K+] <3.5 mmol/L
Treatment of hypokalemia
Treat underlying cause. Withdraw harmful medication. Normalise magnesium as well as potassium.
Mild hypokalaemia - oral K+
Severe hypokalaemia - IV K+
Complication of hypokalemia
Cardiac arrhythmia and sudden death
*Describe prolactinoma
Benign adenoma of the pituitary gland producing prolactin
Types of Prolactinoma and which is more common
Micro (most common >90%)
Macro (>10mm)
Clinical presentation of prolactinoma
Local effect of the tumour: headache, visual field defect (macroprolacinoma only).
Effects of prolactin (hyperprolactinaemia): menstrual irregularity, infertility, galactorrhoea, hypogonadism
Pathophysiology of prolactinoma
Increased release of prolactin can cause galactorrhoea by stimulating milk production from mammary gland, as well as inhibit FSH and LH.
Additionally, it causes secondary hypogonadism, reduced libido and sexual dysfunction in men.
Dopamine has an inhibitory effect on prolactin.
Pituitary tumour is located near to the optic chiasm -> visual field disturbances.
Very rarely malignant.
Aetiology of prolactinoma
Prolactinoma: Cause unknown. Some genetic association.
Other causes of Hyperprolactinaemia: Non functioning pituitary tumour; compress pituitary stalk -> no inhibition of prolactin release; Antidopaminergic drugs;
Head injury -> damage to the pituitary stalk
Diagnostic tests of prolactinoma
Check prolactin
Treatment of prolactinoma
Dopamine agonist (cabergoline). Transphenoidal pituitary resection.
*Describe Pheochromocytoma
Catecholamine (adrenaline) secreting tumour
Clinical presentation of Pheochromocytoma
Episodic.
Headaches, palpitations, sweating, tremor, anxiety, nausea and weight loss.
Hypertension, tachycardia and pallor.
Types of Pheochromocytoma
Familial type: More noradrenaline
Sporadic: More adrenaline
Pathophysiology of Pheochromocytoma
Catecholamine producing tumours of the chromafin cells of the medulla
Aetiology of Pheochromocytoma
Inherited or spontaneous. Sometimes associated with multiple endocrine neoplasia.
Epidemiology of Pheochromocytoma
10% malignant
Diagnostic tests of Pheochromocytoma
24hr urine collection for urinary catecholamines and metabolites (metanephrines). Plasma catecholamines (not as sensitive)
Treatment of Pheochromocytoma
Surgery (preceded by alpha and beta blocker to stagger adrenaline loss (alpha first, if beta at all))
Complication of Pheochromocytoma
Can stroke out during surgery, due to the rapid effect of adrenaline on the BP
*Describe carcinoid tumour
Serotonin secreting tumour.
Tend to express somatostatin receptors.
Types of carcinoid tumours
Foregut
Midgut
Hindgut
Clinical presentation of carcinoid tumour
Most clinically silent, can cause pain, weight loss or a palpable mass.
Carcinoid syndrome: Bronchospasm, diarrhoea, skin flushing and right sided heart lesions
What is a common place of a carcinoid tumour of lung, bowel or stomach to metastasise to?
Liver
only symptomatic with liver metastasises
Pathophysiology of carcinoid tumour
Derived from enterochromaffin cells. Can also be in the gallbladder, kidney, liver, pancreas and gonads.
They tend to secrete bioactive compounds, including serotonin and Kallikrein (lead to increase in bradykinin), which cause carcinoid syndrome.
GI carcinoid tumours only cause this if they metastasise to liver, where the products can drain into the heaptic vein.
Diagnostic tests of carcinoid tumour
Urine: High volume of 5-hydroxyindoleacetic acid (breakdown product of serotonin).
Liver ultrasound: Confirm metastases
Octreoscan: Radiolabelled ocreotide (somatostatin analogue) hits the somatostatin receptors
Treatment of carcinoid tumour
Somatostatin analogue (octreotide). Surgical resection, to reduce tumour mass
What conditions increase the incidence of carcinoid tumours?
MEN 1 (Multiple Endocrine Neoplasia)
MEN 2
Von-Hippel Lindau
Why would a patient be more likely to first approach a dr in later stages of a carcinoid tumour
Only symptomatic with liver metastasises
What cells do carcinoid tumours derive from?
Enterochromaffin cells
Describe Graves’ Opthalmopathy
Presents in most Graves’ and some autoimmune hypothyroidism patients
Results in retro-orbital inflammation and swelling of the extrocular muscles
Eye discomfort, grittiness, increased tear production, photophobia, diplopia, reduced acuity
Exophthalmos - appearance of protruding eye and proptosis - eye protrudes beyond orbit
Conjunctival oedema
Corneal ulceration
Ophthalmoplegia - paralysis of eye muscles
Describe treatment of Graves’ Opthalmopathy
Conservative treatment includes smoking cessation and sunglasses
Treated with IV METHYLPREDNISOLONE and surgical decompression or eyelid surgery
How are eyes examined for Graves’ opthalmopathy (except seeing it for yourself)
CT or MRI of orbit
Describe Graves’ dermopathy
Rare
Pretibial myxoedema
Thyroid acropachy
*What is pretibial myxoedema
raised, purple-red symmetrical skin lesions over the anterolateral aspects of the shin
What is thyroid acropachy
clubbing, swollen fingers and periosteal bone formation
When would you see toxic multi nodular goitre?
Elderly - common older women
Iodine-deficient areas
(drug therapy rarely produces prolonged remission)
*What is toxic multi nodular goitre?
nodules that secrete thyroid hormones
see mind maps hyperthyroidism
What % of hyperthyroidism cases are solitary toxic adenoma/nodule
5%
What is De Quervain’s Thyroiditis
Type of transient hyperthyroidism
Acute inflammation of the thyroid gland
What causes De Quervains Thyroiditis
Acute inflammation of thyroid gland, generally due to viral infection
Describe diagnosis of De Quervains Thyroiditis
Typical for there to be globally reduced uptake on technetium thyroidscan
Usually accompanied by fever, malaise and pain in the neck
Treatment of De Quervains Thyroiditis
Aspirin
Prednisolone for severely symptomatic cases
What drugs can cause hyperthyroidism?
AMIODARONE (anti-arrhythmic drug) - due to high iodine content
Iodine
Lithium
Why can amiodarone also cause hypothyroidism
Inhibits conversion of T4 to T3
Clinical presentation of hyperthyroidism specific to elderly
Atrial fibrillation
Tahcycardias and/or heart failure
Clinical presentation of hyperthyroidism specific to young
Excessive height or excessive growth rate
Behavioural problems like hyperactivity
Clinical presentation of Graves disease
Palpitations Diarrhoea Weight loss and increased appetite Oligomenorrhoea +/- infertility Heat intolerance i.e. sweating a lot Irritability/behavioural change Tremor Hyperkinesis Warm (vasodilator peripheries) Proximal myopathy and muscle wasting Anxiety Lymphadenopathy and Splenomegaly can occur Diffuse goitre Lid lag and stare
What is oligomenorrhoea
infrequent periods
What is hyperkinesis
muscle spasm
Describe clinical presentation of hyperthyroidism in the hands
Palmar erythema
Warm moist skin
Fine tremor
How does differential diagnosis of hyperthyroidism differ to mid anxiety
Eye signs e.g. lid lag & stare
Diffuse goitre
Proximal myopathy and wasting
How could you differentiate Graves form toxic adenoma
Ultrasound of thyroid
Diagnosis of hyperthyroidism
Thyroid function tests (TFTs) (serum TSH is suppressed due to negative feedback, but T4 and T3 raised) Thyroid peroxidase (TPO) and thyroglobulin antibodies (also presents tin 80% of Graves cases)
Treatment of hyperthyroidism
Beta-Blockers e.g. propranolol for rapid control of symptoms
Anti-Thyroid drugs e.g. propylthiouracil or oral carbimazole
Radioactive iodine (131)
Surgery (thyroidectomy)
What are 2 strategies for treatment of hyperthyroidism using anti-thyroid drugs
Titration e.g. ORAL CARBIMAZOLE for 4 wks then reduce doses according to thyroid function tests (TFTs; TSH, T3 & T4)
Block-replace therapy e.g. ORAL CARBIMAZOLE + THYROXINE (T4) which has less risk of developing hypothyroidism
What is main side effect of anti-thyroid drugs like propylathiouracil or carbimazole
Agranulocytosis:
Results in leukopenia
If get sore throat, mouth ulcers and fevers then stop drug asap
Side effects of anti-thyroid drugs
Agranulocytosis Rash Arthralgia Hepatitis Vasculitis
How does anti-thyroid drug Propylthiouracil work?
Stops the conversion of T4 to T3
How does anti-thyroid drug Carbimazole (oral) work?
Blocks thyroid hormone biosynthesis and has immunosuppressive effects (which will affect Graves’ disease process)
Radioactive I (131): contraindications and side effects
CI in pregnancy and breast feeding
SEs indue discomfort in the neck and hyperthyroidism initially
Can be given to all ages
Stop antithyroid drugs 4 days before giving iodine
How does radioactive iodine (131) treatment work for hyperthyroidism
Iodine is essential for thyroid hormone production so is readily taken up by the thyroid gland
Here it accumulates and results in local irradiation and tissue damage with return to normal thyroid function over 4-12 weeks
When would you undergo surgery for hyperthyroidism
Those with large goitre, poor response to drugs and have drug side-effects
When would you undergo a subtotal and when a total thyroidectomy
Subtotal thyroidectomy only in those who have been rendered euthyroid (normal functioning thyroid gland)
Total thyroidectomy only in those with large goitre or suspicion of malignancy (toxic adenoma) in a nodule and also for Graves’
Complications of surgery for hyperthyroidism
Hypothyroidism
Tracheal compression from postoperative bleeding
Laryngeal nerve palsy resulting in hoarse voice
Transient hypocalcaemia - due to removal of parathyroid gland too
Complications of hyperthyroidism if untreated
Thyroid crisis or thyroid storm
Rare life threatening condition
Rapid deterioration of thyrotoxicosis (rapid T4 increase)
Describe features of thyroid crisis or thyroid storm
hyperpyrexia, tachycardia, extreme restlessness
and eventually delirium, coma and death
Usually precipitated by stress, infection, surgery or radioactive iodine therapy in an unprepared patient
Treatment of thyroid crisis or thyroid storm or untreated hyperthyroidism
Large doses of:
- ORAL CARBIMAZOLE
- ORAL PROPRANOLOL
- ORAL POTASSIUM IODIDE (to block acutely the release of thyroid hormone from gland)
- IV HYDROCORTISONE (to inhibits peripheral conversion of T4 to T3)
Symptoms of hypothyroidism
- Hoarse voice
- Goitre
- Constipation
- Cold intolerant
- Weight gain
- Menorrhagia
- Myalgia, weakness
- Tired, low mood, dementia
- Myxoedema - accumulation of mucopolysaccharide in SC tissue
Signs of hypothyroidism
BRADYCARDIC: • Bradycardia • Reflexes relax slowly • Ataxia (cerebellar) • Dry, thin hair/skin • Yawning/drowsy/coma • Cold hands +/- temperature drop • Ascites • Round puffy face • Defeated demeanour • Immobile +/- Ileus (temporary arrest of intestinal peristalsis) • Congestive cardiac failure
Primary cause of hypothyroidism
Disease of the thyroid gland
Secondary cause of hypothyroidism
Hypothalamic or pituitary disease
leads to thyroid disease
What % of the population is affected by hypothyroidism and what gender is more affected
0.1-0.2%
females
Main cause of primary hypothyroidism
Iodine deficiency
What genetic diseases associate with hypothyroidism
Turners*
Downs syndrome
Cystic fibrosis
Others:
Primary biliary cirrhosis
Ovarian hyper-stimulation
In Hashimoto’s thyroiditis, describe thyroid gland appearance/feel
Gland is usually firm and rubbery but may range from soft to hard
In Hashimoto’s thyroiditis, what causes goitre
Atrophic changes with regeneration result in GOITRE FORMATION due to lymphocytic and plasma cell infiltration
What causes postpartum thyroiditis
Modifications to immune system necessary in pregnancy and histologically is a lymphocytes thyroiditis
What can postpartum thyroiditis be misdiagnosed as?
Postpartum depression
therefore TFTs are essential to confirm diagnosis
what is meant by iatrogenic?
caused by treatment or examination
What iatrogenic factors can lead to hypothyroidism
Thyroidectomy (for treatment of hyperthyroidism or goitre)
Radioactive iodine treatment or external neck irradiation for head and neck cancer
*What drugs can induce to hypothyroidism
Carbimazole
Lithium
Amiodarone (hyper or hypothyroidism)
Interferon
Why can amiodarone cause hyper or hypothyroidism
Hyper - due to high iodine content
Hypo - as inhibits the conversion of T4 to T3
What can result from dietary iodine deficiency?
Goitre
Patients have are euthyroid or hypothyroid, depending on the severity of iodine deficiency
Where is iodine deficiency an issue in the world
Netherlands Western Pacific India SE Asia Russia some Africa
*What is myxoedema?
Accumulation of mucopolysaccharide in SC tissue
Swelling of the skin and underlying tissues giving a waxy consistency, typical of patients with underactive thyroid glands
Presentation of hypothyroidism in children
Slow growth velocity
Poor school performance
Sometime puberty arrest
may not show classic features
Why is diagnosis of hypothyroidism in elderly difficult
Hard to differentiate clinical features from normal ageing
Give example of lifelong thyroid hormone replacement drug
Oral Levothyroxine (T4)
What would be seen in a blood test of hypothyroidism
Raised serum aspartate transferase levels from muscle and/or liver
Increase serum creatinine kinase levels associated with myopathy Hypercholesterolaemia
Hyponatraemia due to an increase in ADH and impaired free water clearance
Complication of Hypothyroidism is Myxoedema coma, what is given in hospital to treat this?
IV/Oral T3
Glucose infusion
In treating hypothyroidism with Levothyroxine, what important things must you bear in mind
Patients with IHD use with caution and start on lower dose
Don’t give too much as completely suppresses TSH as this carries risk of AF and osteoporosis
What can occur from Levothyroxine overdose?
Can completely suppress TSH
Risk of AF and osteoporosis
How can you monitor treatment of primary hypothyroidism?
Check T4 levels 6-8 weeks after dose adjustment
How can you monitor treatment of secondary hypothyroidism?
TSH will always be low
T4 is monitored
**General treatment of thyroid cancer
Radioactive iodine (will locally irradiate and destroy cancer - providing very little radiation damage to other surrounding structures)
Levothyroxine (T4) to keep TSH reduced as this is a risk factor
Chemotherapy helps reduce risk of spread and treats micro-metastases
What is CRH
Corticotropin Releasing hormone
Where is CRH released from
Hypothalamus
CRH causes the release of what hormone
ACTH
Adrenocorticotrophic hormone
from anterior pituitary
What is the function of ACTH
Stimulates cortisol and androgen production by the adrenal cortex
Will aldosterone secretion be affected by disease of hypothalamus or pituitary?
No as aldosterone secretion responds to renin release by the juxtaglomerular cells of afferent arterioles kidney
Only pathology of kidney would
Are the adrenal glands intra or retro-peritoneal
Retroperitoneal
What are the 3 layers of adrenal cortex and what does each secrete
Zona glomerulosa - Mineralocorticoids e.g. aldosterone
Zona fasciculata - Glucocorticoids e.g. cortisol
Zona reticularis - Androgens (sex hormone)
(Makes Good Sex)
What are all the layers of adrenal gland in order of most superficial to most deep
Capsule Zona glomerulosa Zona fasciculata Zona reticularis Adrenal medulla
Androgens released by zone reticularis are converted to what peripherally
Testosterone
Dihydrotestosterone
What does adrenal medulla secrete
Catecholamines e.g. Adrenaline or Noradrenaline
under sympathetic control
Excess of what drug can mimic Cushings Disease?
Alcohol
*What are the functions of cortisol
- Increased carbohydrate and protein catabolism (breakdown)
- Increased deposition of fat and glycogen
- Na+ retention
- Increased renal K+ loss
- Diminished host response to infection
Describe when corticotrophin and thus cortisol levels are highest and lowest
Released according to a Circadian Rhythm and stress
Highest levels in morning 7/9am
Lowest at midnight
Give examples of things that can cause high-cortisol
Alcohol pseudo-Cushings syndrome Depression Obesity Pregnancy (Stress also)
Why do you get infections in Cushings syndrome more easily?
Anti-inflammatory effect of cortisol and poor healing
Differential diagnosis of Cushings syndrome
Pseudo-Cushing’s syndrome - caused by alcohol excess, resolves after 1-3 weeks of alcohol abstinence
Diagnosis of Cushings
Drug history - oral steroids?
Random plasma cortisol
1st line test: Dexamethasone overnight suppression test (normally causes cortisol depression but this is not the case in cushings) or Urine free cortisol test over 24 hours
2nd line test:
if no suppression
48 hour
Aetiology of hyperthyroidism
2/3 cases are Graves Disease
Toxic multi nodular goitre
Toxic thyroid adenoma
Iodine excess congenital (less common)
Symptoms of hyperthyroidism
(like how you feel before an exam) Diarrhoea Weight loss Sweats Heat intolerance Palpitations Tremor Anxiety Menstrual disturbance
Signs of hyperthyroidism
Tachycardia Thin hair Lid lag Lid retraction Onycholysis Exophthalmos
Investigations of hyperthyoridism
TFTs (thyroid function test) Thyroid autoantibodies (Thyroid peroxidase, thyroglobulin, TSH receptor antibody) Radioactive iodine isotope uptake scan
What would a TFT show in primary hyperthyroidism
Low TSH
High T3/T4
What would a TFT show in secondary hyperthyroidism
High TSH
High T3/T4
Describe Graves Ophthalmology appearance
Extraocular muscle swelling
Eye discomfort
Lacrimation
Diplopia
Define gigantism
Increased production of GH occurring in children
Symptoms of acromegaly
Acroparaesthesia, Arthralgia, Sweating, Decreased libido, Headache
Signs of acromegaly
Massive growth of the hands, feet and jaw Big tongue with widely spaced teeth Puffy lips, eyelids and skin Darkening skin Obstructive sleep apnoea Deep voice
What is acroparaesthesia
pins and needles in extremities
Why do you not do a growth hormone measurement to investigate if patient has acromegaly
GH is a pulsatile protein and levels vary throughout day
Do oral glucose tolerance test
Describe ECG of Conns syndrome
Flat T
Long PR
Long QT
U waves
What is pseudohypoparathyroidism
Decreased response to PTH
Bloodwork shows low Ca, high PTH
Treat as normal hypoparathyroid
What hormone stimulates the secretion of potassium in the kidney?
Aldosterone
Is hypokalaemia a result of high or low aldosterone
High aldosterone
More K excretion
Less K in body
Hyperkalemia is a result of low aldosterone. What can therefore cause hyperkalemia
Low aldosterone - adrenal insufficiency
ACE inhibitors - block the binding of aldosterone to receptor
AKI - decreased fibrillation rate so more K+is maintained in the blood
What is the role of K in the body
Charged and Helps maintain the resting potential of all muscles in the body
Hypokalaemia - describe effects on muscles
Everything slows
Smooth - constipation
Skeletal - Weakness/cramps
Cardiac - Arrhythmias and palpitations
Hyperkalaemia - describe effects on muscles
Everything speeds up Smooth - cramping Skeletal - Weakness/ flaccid paralysis Due to over contraction muscles become totally drained of energy Cardiac - Arrhythmias and arrest
How does insulin affect potassium balance
Excess insulin -> Hypokalaemia
too much K+ follows insulin into cell
Insulin deficient -> Hyperkalemia
Not enough K+ follows into the cell
**How does pH change with potassium balance
Alkalosis (high pH) -> H+ out of cell and K+ in -> hypokalaemia
Acidosis (low pH) -> H+ into cell and K+ out ->Hyperkalemia
(decrease K+ by replacing with H+)
How do drugs acting on the Beta 2 receptor affect potassium balance
B2 agonists (SABA/LABA) -> increase B2 pumping of K+ into cell -> Hypokalaemia
Beta blocker -> inhibits pumping of K+ into cell -> Hyperkalemia
How does cell lysis cause potassium balance issues
Intracellular contents released as get Hyperkalaemia
Severe burns or tumour lysis syndrome for example
Symptoms of hypocalcaemia
SPASM Spasms Peripheral paraesthesia Anxious Seizures Muscle tone increase
Signs of hypocalcaemia
CATS Convulsion Arrhythmias Tetany Spasm and Stridor
ECG of hypocalcaemia
Long QT interval
What malignancies cause hypercalcaemia?
Myeloma
Non-hodgkin lymphoma
What is difference between Cushings syndrome and disease?
Both involve:
Excess cortisol
Loss of hypothalamic pituitary axis feedback
Loss of circadian rhythm
C Disease also caused by pituitary adenoma
How can an Adrenalectomy lead to Nelson’s syndrome
If you remove the adrenal glands then no cortisol will be produced in response to ACTH produced by the pituitary gland.
If no cortisol is produced then there is no negative feedback on ACTH levels which can cause ACTH to build up in the body tissues.
This can cause a bronze pigmentation of the skin, visual disturbances and headaches.
a 16yr old female, presents to A&E with her mother after feeling vey weak and experiencing some palpitations. Her mother is concerned that her daughter is very skinny, you check her BMI and it is 16.What is the most likely cause of her condition?
Hypokalaemia
Hyperkalaemia
Hypocalcaemia
Hypercalcemia
Hypokalemia
anorexic BMI
a 73 year old gentleman presents to his GP for some routine tests following a recent diagnosis of secondary hyperparathyroidism. All the results get mixed up in the pile which one is Jims?
A) Calcium high, Phosphate high, ALP high
B) Calcium low, phosphate low, ALP low
C) Calcium low, Phosphate high, ALP high
D) Calcium low, phosphate low, ALP high
A- tertiary
B Nothing
*C- secondary
D- primary
A 29yo man presents with 4-week history of polyuria and extreme thirst. The urine is very dilute. The patient does not have any weight loss and maintains a good diet. No findings are found on urine dipstick. The most appropriate invevstigation is:
Serum osmolality Fasting plasma glucose Urinary electrolytes MRI head Water deprivation test
*Water deprivation test = Diagnostic for DI
The initial treatment for somebody having a thyrotoxic storm (hyperthyroid crisis) is:
IV 0.9% saline Propanolol Salbutamol Carbimazole Omeprazole
Propanolol
(Carbimazole long term)
saline would probably be given but isn’t going to have much of an effect, salbutamol is for asthma / respiratory disease, carbimazole is an antithyroid treatment and would probably be given too but does not help immediately with symptoms, and omeprazole is a PPI. Therefore the best initial treatment is propanolol, a beta blocker
Hypocalcaemia
Chvostek’s sign is the twitching of the facial muscles in response to tapping over the area of the facial nerve.
Trousseau’s sign is carpopedal spasm caused by inflating the blood-pressure cuff to a level above systolic pressure for 3 minutes.