ENDOCRINE: Electrolyte abnormalities incl parathyroid Flashcards
SIADH, calcium NEED TO ADD MORE ON PARATHYROIDISM
What is the relevance of hyponatraemia?
Very commonly affects hospital patients, up to 30% of hosp patients will have hyponatraemia
Hyponatraemia is characterised by a low concentration of sodium in the serum, specifically less than 135mmol/L.
What are the symptoms of hyponatraemia?
Early symptoms: headache nausea vomitting general malaise
Later signs:
confusion
agitation
drowsiness
What serious symptoms can acute severe hyponatraemia cause?
Seizures
Resp depression
Coma
Death
What common medication can cause hyponatraemia?
thiazide like diuretics
ACEi
SSRIs
Furosemide
What is osmolality?
How salty the blood is, low osmolality means less salt
What is a complication of acute severe hyponatraemia?
cerebral oedema
In patient with severe acute hyponatraemia what would always prescribe?
Hypertonic saline
What are the hallmark biochemical features of primary adrenal failure?
Hyperkalaemia, hyponatraemia, raised urea and mild anaemia, hypoglycaemia
What biochemical investigations would you do in a patient with hyponatraemia?
Serum osmolality, urine osmolality, urine sodium, thyroid function and assessment of cortisol response
What is the first thing to do if a patient presents with low serum osmolality?
Rule out non-hypo- osmolar hyponatraemia e.g. hyperglycaemia
What would a low serum osmolality and urine osmolality of less than 100mosmol/kg indicate?
primary polydipsia or inappropriate IV fluid administration
What is the next steps in investigation if a patient has low serum osmolality and a urine osmolality of greater than 100mosmol/kg?
You need to measure their urine sodium
What would a low serum osmolality and a urine osmolality of greater than 100mosmol/kg (100= concentrated) and urine sodium of less than 30mmol/kg?
True dehydration e.g. GI salt loss
OR
clinically overloaded but intravascular depletion e.g. in congestive cardiac failure, cirrhosis or nephrotic syndrome
Urine sodium of <30 mmol/L suggests low effective arterial volume
What would a patient with SIADH look like biochemically (serum osmolality, urine osmolality, urine sodium and their fluid balance)
Low serum osmolality
Urine osmolality> 100mosmol/kg
Urine sodium> 30mmol/L
Euvolaemic
What is the next steps in investigation if a patient has low serum osmolality and a urine osmolality of greater than 100mosmol/kg and urine sodium of greater than 30mmol/kg?
Need to work out - are they EUVOLAEMIC or DEHYDRATED?
A patient low serum osmolality and a urine osmolality of greater than 100mosmol/kg and urine sodium of greater than 30mmol/kg and they are dehydrated, what do you need to consider?
Addison’s disease, renal or cerebral salt wasting or does the patient have a history of vomitting
What do you need to rule out before you make a diagnosis of SIADH?
Hypothyroidism - elevated ADH due to decreased Cardiac output
Total salt depletion
ACTH deficiency- check serum cortisol as low cortisol causes less -ve feedback on CRH and Cortisol directly suppresses ADH secretion )
Why does ACTH deficiency present like SIADH?
Cortisol deficiency leads to increased ADH secretion
What are the causes of SIADH?
- Pituitary tumour
- Tumours: small cell lung cancer, thymoma, lymphoma
- Pulmonary disease: infections, pneumothorax, asthma, cystic fibrosis
- CNS disease: infection (SE of meningitis/encephalitis), head injury
- Drugs: chemotherapy, psychiatric drugs (lithium = nephrogenic cause)
- Idiopathic
What malignancy is know to cause SIADH?
small cell lung cancer
How do you treat SIADH?
Fluid restriction- however in practice this is quite poorly tolerated
ADH antagonists- Tolvaptan
Demeclocycine- tetracycline antibiotic that inhibits ADH
How do you treat hyponatraemia?
Hypovolaemic hyponatraemia- normal saline
Hypervolaemic hyponatraemia- needs specialist treatment to treat the underlying cause of CCF, nephrotic syndrome or cirrhosis
What is Trousseau’s sign? What is relevance?
Due to Hypocalcaemia
When inflate BP cuff above systolic pressure. Brachial artery is occluded. Causes carpal spasm (e.g. wrist flexing and fingers abducting)
What is Chvostek’s sign? What is its relevance?
Due to hypocalcaemia.
Tapping over parotid (CN7) causes facial muscles to twitch
Define hypoparathyroidism
- medical condition characterized by abnormally low levels of parathyroid hormone (PTH)
- this leads to disturbances in calcium and phosphorus metabolism.
- It can be primary (due to parathyroid gland dysfunction) or secondary (resulting from other medical conditions or treatments).
Risk factors for Hypoparathyroidism
- Neck surgery or radiation therapy involving the parathyroid glands.
- Autoimmune conditions, such as autoimmune polyendocrine syndrome.
- Genetic factors and familial forms of the condition
Pathophysiology of hypoparathyroidism?
- Decreased PTH production or function > disrupts calcium and phosphorus homeostasis.
- This leads to decreased calcium absorption from the intestines, reduced bone resorption, and impaired renal reabsorption of calcium.
What are the main symptoms of hypoparathyroidism?
- Hypocalcemia-related manifestations: muscle cramps, perioral and others paresthesias, tetany, and seizures.
-Trousseau’s sign: carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
-Chvostek’s sign: tapping over parotid causes facial muscles to twitch
- Neuropsychiatric symptoms: anxiety, depression, and cognitive impairment
- Ocular symptoms: cataracts (chronic hypoparathyroidism) and impaired night vision
- Dental abnormalities: dental enamel hypoplasia and tooth discoloration
Differenicals for hypoparathyroidism?
Distinguishing hypoparathyroidism from other medical conditions with similar symptoms is essential, including:
- Hypocalcemia due to other causes (e.g. renal failure)
- Vitamin D deficiency
- Neuromuscular disorders
- Psychiatric conditions
Diagnostic investigations for hypoparathyroidism?
- Serum calcium (low) and phosphate levels (high)
- Measurement of PTH levels (low/inappropriately normal)
- Assessment of vitamin D status
- Urinary calcium may be low
- ECG to detect cardiac abnormalities due to hypocalcaemia - prolonged QT
Management of hypoparathyroidism?
- Oral calcium and active vit D (calcitriol) to maintain low-normal calcium levels. This is to avoid renal complications
- Regular Monitoring: Ongoing monitoring of calcium levels and PTH
- Addressing Symptoms: Symptomatic management of neuromuscular and psychological symptoms
- Potential Surgery: Parathyroid gland autotransplantation or glandular tissue implantation in refractory cases
- In acute severe hypocalcaemia, treatement with IV calcium may be required
Complicaitons of hypoparathyroidism?
- Severe hypocalcemia leading to seizures and cardiac arrhythmias
- Kidney stones due to increased urinary calcium excretion
- Impaired renal function
- Cataracts
- Neurological and neuropsychiatric sequelae
What is Pseudohypoparathyroidism?
how is this different from hypoparathyroidism?
- Rare genetic disorder where the target organs (bone, kidney, and gut) fail to respond to normal levels of parathyroid hormone due to defects in the PTH receptor.
- This is in contrast to hypoparathyroidism, in which there is a deficiency of the parathyroid hormone itself.
Cause of Pseudohypoparathyroidism
Pseudohypoparathyroidism is most commonly due to mutations in the GNAS1 gene, which codes for the alpha subunit of the Gs protein. This protein is vital for PTH to exert its action on its target cells.
Similar to that of hypoparathyroidism and includes:
- Short stature and shortened 4th and 5th metacarpals in fingers
- Hypocalcemia leading to:
- Numbness or tingling of the fingers and toes
- Muscle cramps
- Carpopedal spasm
- Seizures
- Chvostek’s sign: Twitching of the face after tapping the facial nerve
- Trousseau’s sign: Carpopedal spasm after inflating a blood pressure cuff
- Symptoms related to vitamin D deficiency such as bone pain and fractures
Differencials for pseudohypoparathyroidism?
- Hypoparathyroidism: Shares similar symptoms but is characterized by deficient parathyroid hormone.
- Vitamin D deficiency: Presents with bone pain and fractures but lacks other symptoms related to hypocalcemia.
- Hypocalcemia due to other causes such as kidney disease or malnutrition.
Investigations for pseudohypoparathyroidism?
mainly clinical, supported by biochemical findings:
- Hypocalcemia on serum calcium levels
- Normal or elevated levels of parathyroid hormone
Management of pseudohypoparathyroidism?
mirrors that of hypoparathyroidism, with the focus being on managing hypocalcemia and maintaining normal serum calcium levels. This includes:
*
* Calcium supplementation
* Vitamin D supplementation
Define hypercalcaemia?
Hypercalcaemia is a medical condition defined as having a corrected calcium level greater than 2.65mmol/L.
Causes of Hypercalcaemia?
90% of the times the causes are:
primary hyperparathyroidism or cancer
other causes:
* sarcoidosis (other causes of granulomas may lead to hypercalcaemia e.g. tuberculosis and histoplasmosis)
* vitamin D intoxication
* acromegaly
* thyrotoxicosis
* Milk-alkali syndrome
* drugs: thiazides / ca containing antacids
* dehydration
* Addison’s disease
* Paget’s disease of the bone ( if prolonged immobilisation)
Explain the processses of how malignancy can lead to hypercalacaemia?
what key investigation is needed for working out the cause?
This may be due to a number of processes, including;
* PTHrP from the tumour e.g. squamous cell lung cancer
* bone metastases
* myeloma,: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
KEY INVESTIGATION: measuring parathyroid hormone levels is the key investigation for patients with hypercalcaemia
How does hypercalcaemia present?
- ‘bones, stones, groans and psychic moans’
- polyuria, polydipsia
- corneal calcification
- shortened QT interval on ECG
- hypertension
Investigatoins for hypercalacaemia?
Bedside:
* ECG: shortened QTc may be present
* Urinary calcium levels
Lab:
* Bone profile (calcium, phosphate, albumin, total protein, ALP)
* Parathyroid hormone levels
* Myeloma screen: serum protein electrophoresis, serum free light chains/urinary bence jones proteins, full blood count (for anaemia)
* Sarcoidosis: serum ACE
Imaging:
- Bone scan/PET scan (malignancy)
- CXR chest radiograph showing bilateral hilar lymphadenopathy for Sarcoidosis
Treatment of hypercalcaemia?
Acute hypercalcaemia
* IV fluids with crystalloid to help improve calcium excretion and protect the kidneys from injury
Following fluid resuscitation
* bisphosphanates (hypercalcaemia of malignancy) to reduce osteoclastic activity (e.g. IV Zoledronate.)
* Calcitonin is second line.
- Steroids in sarcoidosis
- Furosemide helps increase calcium excretion in the kidney and may also be used in the acute setting
Define hypocalcaemia?
Hypocalcaemia is an electrolyte imbalance where the circulating serum calcium level is less than 2.1mmol/L.
During hypocalcaemia, the total calcium level and the ionised calcium level fall below the laboratory reference range.
Pathophysiology of hypocalacemia?
- In hypocalcaemia, the parathyroid hormone (PTH) axis plays a vital role in maintaining calcium balance.
- When blood calcium levels drop, the parathyroid glands release PTH.
- PTH acts on the bones, kidneys, and intestines.
- It stimulates bone resorption to release calcium, enhances renal calcium reabsorption while increasing phosphate excretion, and activates vitamin D in the kidneys to boost calcium absorption from the gut.
- These actions collectively raise blood calcium levels, restoring homeostasis.
The causes of hypocalcaemia can be complex. They can be grouped as follows:
Hypocalcaemia with LOW PTH
Hypocalcaemia with HIGH PTH
Hypocalcaemia due to compartmental shifts
What are causes of Hypocalcaemia with inappropriately LOW PTH
Destruction of parathyroid glands
* Surgery, autoimmune, radiation, infiltration (iron, copper, tumour e.g. sarcoid, haemachromatosis, amyloidosis, granulomatous disorders, Wilson’s, neoplasia)
Developmental parathyroid disorders
* Isolated hypoparathyroidism
* Autosomal recessive, autosomal dominant, or X-linked syndromes
* Syndromes of hypoparathyroidism (e.g., DiGeorge sequence)
* Reduced PTH secretion/function
* Hypomagnesaemia
* Hungry bone disease following parathyroidectomy.
*
The causes of hypocalcaemia can be complex. They can be grouped as follows:
Hypocalcaemia with LOW PTH
Hypocalcaemia with HIGH PTH
Hypocalcaemia due to compartmental shifts
What are causes of Hypocalcaemia with HIGH PTH
- Vitamin D deficiency
e.g. Inadequate UVB light exposure, poor diet, malabsorption - Chronic renal disease, enzyme-induced drug resistance to PTH
- Pseudohypoparathyroidism
- Hypomagnesaemia
- Resistance to vitamin D
- Mutations in vitamin D receptor (mutations in 1-alpha hydroxylase enzyme).
The causes of hypocalcaemia can be complex. They can be grouped as follows:
Hypocalcaemia with LOW PTH
Hypocalcaemia with HIGH PTH
Hypocalcaemia due to compartmental shifts
What are causes of Hypocalcaemia due to compartmental shifts
- Alkalosis
- Massive blood transfusion - citrate is a calcium chelator
- Osteoblastic metastases
- Hyperphosphataemia
- Alkalosis
Severe illness: - Acute pancreatitis
- Acute rhabdomyolysis
- Tumour lysis
- Post massive transfusion.
What are the clinical features of acute severe hypocalcaemia?
Laryngospasm
Prolonged QT interval
Seizures
Clinical features of hypocalcemia ?
SPASMODIC
S – Spasms (Trousseau’s sign)
P – Perioral parasthaesia
A – Anxiety/Irritability
S – Seizures
M – Muscle tone increase (colic, dysphagia)
O– Orientation impairment (i.e. confusion)
D – Dermatitis
I – Impetigo herpetiformis
C – Chvostek’s sign
ECG shows prolonged QTc
How is hypocalcaemia treated?
The underlying cause should be addressed e.g. ensure adequate oral intake, alphacalcifidiol in CKD, replace magnesium
- Mild hypocalcaemia can be treated with oral supplementation
- Severe (ECG changes/clinical features) requires intravenous replacement with calcium gluconate
How is acute hypocalcaemia treated?
Severe (ECG changes/clinical features) requires IV replacement with calcium gluconate
What is dosage given for severe vit d deficiency?
Loading dose of cholecalciferol - 20,000IU per week for 7 weeks then maintenance dose of 1-2000 IU per week
What is the aim in treating hypocalcaemia?
Keep calcium levels at lower end of reference to reduce risk of nephrocalcinosis
What is pseudo-hypoparathyroidism?
Rare condition caused by mutation in G protein coupled to PTH receptor, leading to PTH resistance
How does pseudo-hypoparathyroidism present?
Bloods - Hypocalcaemia, High phosphate
Signs - Short stature, round face, short 4th and 5th metacarpals
What is pseudohypoparathryoidism?
due to abnormality in a G protein
associated with low IQ, short stature, shortened 4th and 5th metacarpals
Blood results for pseudohypoparathryoidism?
low calcium, high phosphate, high PTH
How is pseudohypothyroidism diagnosed?
diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause an increase in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.
Define Hyperparathyroidism?
Hyperparathyroidism (HPT) is a clinical condition resulting from the excessive secretion of parathyroid hormone (PTH).
What 3 classifcations can you group hyperparathyroidism (HPT) into?
It presents in three forms:
* Primary
* Secondary
* Tertiary
Each form has distinct causes and management strategies.
Causes of Primary Hyperparathyroidism (PHPT)
Commonly caused by a:
* parathyroid gland adenoma
* hyperplasia of all four glands
* parathyroid carcinoma.
Causes of Secondary Hyperparathyroidism (SHPT)?
Typically due to:
* vitamin D deficiency
* loss of extracellular calcium
* calcium malabsorption
* abnormal parathyroid hormone activity
* inadequate calcium intake.
Causes of Tertiary Hyperparathyroidism (THPT)?
Occurs after **prolonged secondary hyperparathyroidism **due to conditions like chronic kidney disease.
Signs and symptoms of Hyperparathyroidism?
Hyperparathyroidism often results in hypercalcaemia, which can be remembered using the mnemonic:
- Moans: Painful bones
- Stones: Renal stones
- Groans: Gastrointestinal symptoms (nausea, vomiting, constipation, indigestion)
- Psychiatric Moans: Neurological effects (lethargy, fatigue, memory loss, psychosis, depression)
Differential diagnosis for hyperparathyroidism?
- Hypoparathyroidism: Characterized by hypocalcaemia, hyperphosphatemia, and low levels of PTH.
- Vitamin D deficiency: Can cause hypocalcaemia and secondary hyperparathyroidism.
- CKD: Often leads to secondary or tertiary hyperparathyroidism.
- Multiple endocrine neoplasia (MEN): This inherited disorder can cause hyperplasia of parathyroid glands leading to primary hyperparathyroidism.
Investigating suspected hyperparathyroidisim you test for
* Calcium
* Phosphate
* PTH
* ALP
How would values change based on if Primary, Secondary or tertiary cause?
Investigation results: What would, Calcium, Phosphate, PTH, ALP levels come backs as if cause was:
- Vit D deficiency
- CKD
- Malabsorption
- Psuedoparathyroidms.
Definitive management of Primary Hyperparathyroidism (PHPT)?
Definitive management is parathyroidectomy.
Management of Secondary Hyperparathyroidism (SHPT)?
Address underlying causes; vitamin D supplementation and phosphate binders may be needed.
Management of Tertiary Hyperparathyroidism (THPT)?
Managed with medication like Cinacalcet, a calcimimetic that mimics the action of calcium on tissues, or via total or subtotal parathyroidectomy.
Categorise the causes of of hyponatreamia:
Clue: by fluid status : e.g. Hypovolaemic hyponatraemia
- Hypovolaemic hyponatraemia (caused by a loss of sodium and water, with sodium loss
- Euvolaemic hyponatraemia (total body water increases, but the body’s sodium content stays the same)
- Hypervolaemic hyponatraemia (increase in total body sodium content, but an even greater increase in total body water)
Causes of hyponatraemia due to : Hypovolaemic hyponatraemia (caused by a loss of sodium and water, with sodium loss being greater)
Burns
Excessive sweating
Diarrhoea
Vomiting
Fistulae
Addison’s disease
Causes of hyponatraemia due to : Euvolaemic hyponatraemia (total body water increases, but the body’s sodium content stays the same)
Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
Hypothyroidism
Causes of Hypervolaemic hyponatraemia (increase in total body sodium content, but an even greater increase in total body water)
Renal failure
Heart failure
Liver failure
Nephrotic syndrome
differential diagnosis for hyponatraemia?
give their unqiue signs too
- Addison’s disease: Fatigue, loss of appetite, weight loss, nausea, skin discolouration
- SIADH: Thirst, urination, fatigue, lethargy, irritability
- Hypothyroidism: Fatigue, weight gain, cold intolerance, constipation, dry skin
- Renal failure: Fatigue, decreased urine output, swollen ankles, feet and hands, shortness of breath
- Heart failure: Shortness of breath, fatigue, swollen legs
- Liver failure: Jaundice, bleeding, swollen abdomen, confusion
Investigtions for hyponatraemia?
Bedside:
* Urine and plasma paired osmolalities (while not on diuretics): To demonstrate the inappropriate concentration of the urine
- Urine sodium (while not on diuretics): To demonstrate sodium wasting in the kidneys
- Urine dip: To screen for infection and glomerular pathology
Labs
* U&E’s (while not on diuretics): To confirm hyponatraemia and to exclude mixed electrolyte abnormalities (not seen in SIADH)
- TSH and cortisol: To exclude hypothyroidism (a rare cause of euvolaemic hyponatraemia) and Addison’s disease
Management of hypvolaemia hyponatraemia?
IV normal saline
Treat underlying cause
management of Euvolaemic hyponatraemia
i.e. SIADH, Hypothyroidsim
SIADH:
* Fluid restriction
* ADH receptor antagonists (e.g. tolvaptan, demeclocycline)
* Oral sodium and furosemide
Hypothyroidism:
* Levothyroxine
Management of Hypervolaemic hyponatraemia?
Fluid restriction
Treat underlying cause
Management of severe hyponatraemia (i.e. seizures / coma)?
Why cautious?
- hypertonic (3%) saline can be administered.
- CAUTION due to the risk of central pontine myelinosis and is ideally performed in a critical care setting.
- Overcorrection of sodium faster than 12mmol/L/day can lead to a significant risk of central pontine myelinosis due to fluid shifts.
What are some hypoxia related causes of SIADH?
Pneumonia
Chronic Obstructive Pulmonary Disease (COPD)
Tuberculosis (TB)
What are some causes of SIADH related to Central Nervous System (CNS) diseases:
Meningitis
Stroke
Subarachnoid haemorrhage (SAH)
Head injuries
Brain tumours
Acute psychosis
What are some malignancy related causes of SIADH?
Small cell lung cancer
Pancreatic cancer
Prostate cancer
Thymoma
Lymphoma
What are some drug related causes of SIADH?
Carbamazepine
Selective Serotonin Reuptake Inhibitors (SSRIs)
Opiates
Anti-psychotics
ACEi
