Hyperparathyroidism, Parathyroid Hormone and Calcium Flashcards
(32 cards)
Primary Hyperparathyroidism - Causes
In exams, primary hyperparathyroidism is stereotypically seen in elderly females with an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level. It is most commonly due to a solitary adenoma
Causes of primary hyperparathyroidism 80%: solitary adenoma 15%: hyperplasia 4%: multiple adenoma 1%: carcinoma
Primary Hyperparathyroidism - Features
Features - ‘bones, stones, abdominal groans and psychic moans’
polydipsia, polyuria
peptic ulceration/constipation/pancreatitis
bone pain/fracture
renal stones
depression
hypertension
Primary Hyperparathyroidism - Associations
Associations
- hypertension
- multiple endocrine neoplasia: MEN I and II
Primary Hyperparathyroidism - Ix
Investigations
raised calcium, low phosphate
PTH may be raised or normal
technetium-MIBI subtraction scan
Primary Hyperparathyroidism - Mx
Total Parathyroidectomy
Secondary Hyperparathyroidism - At what level of PTH would you begin supplementation with calcium and vitamin D?
Supplementing calcium and vitamin D in secondary hyperparathyroidism runs the risk of adynamic bone disease if this is begun at less than twice the upper limit of the normal range for PTH. For this reason levels are usually tracked until they cross this threshold, where upon supplementation is commenced. In the event that patients with PTH levels greater than twice the upper limit of normal are left untreated, there is significant risk of progression to tertiary disease, and increased propensity to complications associated with hyperparathyroidism including bone resorption, fracture and ectopic calcification.
Example Question:
A 62-year-old woman with a history of type 1 diabetes and end stage renal failure comes to the renal clinic for review. Over the past few months she has been feeling increasingly lethargic with proximal muscle pains and weakness. She is managed with a basal bolus insulin regime, Examination reveals a blood pressure of 155/82 mmHg, pulse is 70 beats per minute and regular. Chest is clear, there is no ankle swelling. Abdomen is soft and non-tender. You confirm proximal muscle weakness.
Investigations
Hb 101 g/l Na+ 137 mmol/l Bilirubin 11 µmol/l Platelets 95 * 109/l K+ 3.7 mmol/l ALP 185 u/l WBC 8.4 * 109/l Urea 13.2 mmol/l ALT 23 u/l Neuts 5.1 * 109/l Creatinine 382 µmol/l γGT 57 u/l Lymphs 2.1 * 109/l Ca++ 2.1 mmol/l Albumin 30 g/l
You suspect that she has secondary hyperparathyroidism. At what level of PTH would you begin supplementation with calcium and vitamin D?
In the normal range Just above the normal range > Twice the normal range Three times the normal range Four times the normal range
Hypercalcaemia - Causes
Hypercalcaemia: causes
The most common causes of hypercalcaemia are malignancy (bone metastases, myeloma, PTHrP from squamous cell lung cancer) and primary hyperparathyroidism
Other causes include sarcoidosis* vitamin D intoxication acromegaly thyrotoxicosis Milk-alkali syndrome drugs: thiazides, calcium containing antacids dehydration Addison's disease Paget's disease of the bone**
*other causes of granulomas may lead to hypercalcaemia e.g. Tuberculosis and histoplasmosis
**usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation
Hypercalcaemia - Example Question
A 56-year-old lady presents with a 3 month history of abdominal pains, low mood and constipation. Past medical history includes hypertension and depression following the death of her husband 2 years ago. Routine blood tests are performed by the GP and upon review the patient is referred into hospital.
Blood tests are as below:
Hb 100 g/l Na+ 135 mmol/l Platelets 230 * 109/l K+ 4.7 mmol/l WBC 10 * 109/l Urea 6 mmol/l Calcium (adjusted) 2.96 mmol/l Creatinine 110 µmol/l Phosphate 1.35 mmol/l CRP 30 mg/l Albumin 35 g/L
Which diagnostic test should be performed first?
> Parathyroid hormone level Myeloma screen CT chest, abdomen and pelvis Urinary calcium levels Skeletal X-ray
The two main causes of hypercalcaemia are primary hyperparathyroidism and malignancy. Parathyroid hormone level will help to differentiate between these two main differentials and help guide further investigations.
Hyperparathyroidism - Hand Radiograph - Example Description
Bilateral hand radiographs in a middle-aged woman demonstrating generalised osteopenia, erosion of the terminal phalangeal tufts (acro-osteolysis) and subperiosteal resorption of bone particularly the radial aspects of the 2nd and 3rd middle phalanges. These changes are consistent with a diagnosis of hyperparathyroidism.
Primary Hyperparathyroidism - Monitoring: Example Question
A 44-year-old woman is admitted to hospital complaining of a swollen breast for three days. She is otherwise well, having no medical problems. She is diagnosed by the surgical team with a breast abscess, which is drained and she is started on antibiotic treatment. Before being discharged, she is found to have elevated corrected calcium (2.79 mmol/L) and elevated parathyroid hormone (9.5 pmol/L).
She is reviewed by the endocrine team. She does not have any symptoms apart from those related to her breast abscess, and additional examination is unremarkable. Further tests are requested, showing that vitamin D levels are normal, 24-hour urine calcium is normal, and a DEXA scan is normal as well. She is advised to see her GP for annual blood tests for calcium levels and renal function.
She is diagnosed with primary hyperparathyroidism. What additional investigation should be used to monitor her?
24-hour urine calcium annually Breast ultrasound annually Abdominal X-ray annually Abdominal ultrasound every three years > DEXA scan every one to two years
The correct answer is a DEXA scan. This patient has been incidentally found to have primary hyperparathyroidism and has no evidence of indications for parathyroidectomy. Monitoring should include renal function and DEXA scanning to identify any decline in renal function, worsening hypercalcaemia or osteoporosis. Any of these changes would be indications for surgery. Abdominal X-rays and ultrasound scanning may be useful in the acute setting to detect renal stones but are not recommended as monitoring. Urinary calcium useful at diagnosis to exclude hypocalciuric hypercalcaemia.
Source:
‘Hypercalcaemia.’ Clinical Knowledge Summaries. National Institute for Health and Care Excellence, Dec. 2014.
Primary Hyperparathyroidism - Diagnosis and Mx: Example Question
A 45-year-old gentleman presents to clinic for review. Two weeks ago he presented to the emergency department with renal colic. A spiral CT KUB confirmed nephrolithiasis and he was managed conservatively with IV fluids, analgesia and an alpha-blocker. His symptoms resolved entirely and he was discharged.
Blood tests: Hb 142 g/l Platelets 329 * 109/l WBC 6.6 * 109/l Na+ 141 mmol/l K+ 3.8 mmol/l Urea 6.2 mmol/l Creatinine 71 µmol/l Corrected calcium 2.71 mmol/l Parathyroid hormone 10.2 pmol/l
Urine tests (24-hour collection): Urinary calcium 183 mg
How should he be further managed?
Annual monitoring of calcium and renal function Encourage oral fluids Bisphosphonates Vitamin D supplementation > Parathyroidectomy
The correct answer is parathyroidectomy. This is a patient who has developed renal colic secondary to likely primary hyperparathyroidism, as is suggested by his hypercalcaemia and elevated parathyroid hormone. The mainstay of management of primary hyperparathyroidism is parathyroidectomy, but cases have to be appropriately identified as surgical candidates. This patient developed renal stones as a likely complication and therefore would benefit from surgery. If the blood tests been an incidental finding, then monitoring and oral fluids both would have been more appropriate.
Source:
‘Hypercalcaemia.’ Clinical Knowledge Summaries. National Institute for Health and Care Excellence, Dec. 2014
Pseudohyperparathyroidism
Pseudohypoparathyroidism
Pseudohypoparathyroidism is caused by target cell insensitivity to parathyroid hormone (PTH) due to a mutation in a G-protein. In type I pseudohypoparathyroidism
there is a complete receptor defect whereas in type II the cell receptor is intact. Pseudohypoparathyroidism is typically inherited in an autosomal dominant fashion*
Bloods
PTH: high
calcium: low
phosphate: high
Features short fourth and fifth metacarpals short stature cognitive impairment obesity round face
Investigation
infusion of PTH followed by measurement of urinary phosphate and cAMP measurement - this can help differentiate between type I (neither phosphate or cAMP levels rise) and II (cAMP rises but phosphate levels do not change)
*it was previously thought to be an X-linked dominant condition
Pseudohyperparathyroidism Type 1a - Example Question
A surgical Foundation Year 1 doctor (FY1) asks you to review a preoperative ECG for a 19-year-old patient who has been admitted under their team with suspected appendicitis. The only abnormality is a prolonged QT and you note the adjusted calcium to be 2.02 mmol/l.
The FY1 tells you that when they looked at the patients closed fists the outer two knuckles looked like dimples. She also tells you that the patient’s body mass index is 29 kg/m².
You ask her to order some blood tests which come back as follows:
Adjusted calcium 2.02 mmol/l
PTH 69 pmol/L (normal range = 0.8 - 8.5)
Phosphate 2.0 mmol/l
ALP 130 u/l
What is the most likely underlying cause for this patient’s hypocalcaemia?
Hypoparathyroidism > Pseudohypoparathyroidism type 1a Pseudohypoparathyroidism type 1b Pseudopseudohypoparathyroidism Secondary hyperparathyroidism
This patient has a high PTH, a low calcium, a high phosphate and a normal ALP. The patient is also obese and the dimples on the outer two knuckles are likely to represent shortening of the 4th and 5th metacarpals. This biochemistry in combination of these clinical features is characteristic of pseudohypoparathyroidism Type 1a (Albright’s Hereditary Osteodystrophy).
Pseudopseudohypoparathyroidism would have the same clinical features but would have normal biochemistry. Pseudohypoparathyroidism Type 1b would have the same biochemistry but lack the clinical features.
This patient has a high PTH, therefore this immediately excludes hypoparathyroidism. In secondary hyperparathyroidism the ALP would be elevated therefore this is incorrect.
Post Parathyroidectomy Cx - Hypocalcaemia: Example Question
A 50-year-old woman with a history of Grave’s disease is reviewed on the surgical ward some 12hrs after parathyroidectomy. She has begun suffering from episodes of carpopedal spasm and pins and needles affecting both hands and around her mouth. On examination on the ward, her blood pressure is 115/72 mmHg, and pulse is 88 beats per minute. Her serum calcium is measured at 1.85 mmol/l.
Which of the following is the most appropriate intervention?
Intravenous diazepam > Intravenous calcium Intravenous magnesium Oral calcium Oral vitamin D
This patient has symptomatic hypocalcaemia, most likely due to an acute fall in parathyroid hormone after surgery. This is considered a medical emergency and calcium replacement IV is essential:
IV calcium gluconate is administered initially with 20 ml of 10% calcium gluconate in 50-100 ml of 5% dextrose IV, given over 10 minutes with ECG monitoring.This can be repeated until the patient is asymptomatic. It should be followed up with a calcium gluconate infusion where 100ml of 10% calcium gluconate is diluted in 1 litre of normal saline or 5% dextrose and infused at 50-100 ml/hr.
Not intervening with respect to the electrolyte disturbance risks significant sequelae including cardiac arrhythmia, diazepam is therefore not appropriate. IV magnesium is most useful where hypocalcaemia is resistant to correction, and oral interventions would take too long to elevate serum calcium levels.
Hungry Bone Syndrome
Hungry bone syndrome
Hungry bone syndrome is an uncommon entity but can occur after parathyroidectomy if the hyperparathyroidism has been long standing. The mechanism is thought to be thus: high pre-operative levels of parathyroid hormone provide a constant stimulus for osteoclast activity creating the hypercalcaemic state by de-mineralizing the bones. This process can result in x-ray changes very similar to metastatic lytic lesions if left untreated. Upon removal of the parathyroid adenoma the hormone levels fall rapidly (they have a very short half life) and the osteoclast activity is subsequently diminished and the bones rapidly begin re-mineralisation - ‘hungry bone syndrome’. This process can be uncomfortable and also result in systemic hypocalcaemia.
Hungry Bone Syndrome - Example Question
You are asked to review a 67-year-old man who is currently an inpatient on a surgical ward with new paraesthesia in his fingers. He was admitted for an elective parathyroidectomy three days ago for fairly long standing hyperparathyroidism and subsequent hypercalcaemia. He had a single parathyroid adenoma excised which had been identified on pre-operative MIBI scanning. The procedure was without complications but he is now complaining of a tingling sensation in his fingers that he first noticed about twelve hours ago. He also complains of new severe pain in both of his ankles which is worse when he walks, but also present at rest. The surgical SHO has already arranged x-rays of the patient’s ankles and these reveal multiple osteolytic lesions which have been reported as being suspicious for metastatic disease. He is otherwise fit and well and his only regular medications are paracetamol, tramadol and prophylactic dalteparin. His blood tests are as follows.
Adjusted Calcium 1.84 mmol/L
Magnesium 0.7 mmol/L
What is the most likely explanation for his current symptoms?
Metastatic parathyroid cancer Secondary hyperparathyroidism Hypomagnesaemia > Hungry bone syndrome Secondary hypoparathyroidism
Hypocalcaemia after parathyroid surgery is relatively common and usually ‘benign’ and associated with a transient hypoparathyroidism. However, it can sometimes be more marked and give rise to symptoms such as perioral or finger paraesthesia. This state alone would not, however, explain his ankle pain or x-ray findings.
Although hypomagnesaemia may also be present and should be treated, it does not explain the symptoms. Metastatic parathyroid cancer is a possibility given the x-ray findings, but is very uncommon and is less likely given that his hyperparathyroidism and hypercalcaemia was long standing (i.e. indolent). Secondary hyperparathyroidism is the syndrome of appropriately raised parathyroid hormone in response to hypocalcaemia, usually secondary to chronic kidney disease. Secondary hypoparathyroidism describes the normal parathyroid hormone suppression that occurs in hypercalcaemia secondary to non-parathyroid causes, such as malignancy.
Hypercalcaemia - Diagnosis: Example Question
A 60-year-old man attends a medical health check-up at his GP surgery. He was fit and well with a past medical history of childhood asthma and osteoarthritis in his fingers. His observations were included a blood pressure of 129/80 mmHg, pulse of 82 bpm, and oxygen sats of 97%.
Blood tests were performed and revealed:
Hb 138 g/l Platelets 190 * 109/l WBC 7.6 * 109/l Na+ 139 mmol/l K+ 3.9 mmol/l Urea 4.1 mmol/l Creatinine 9.2 µmol/l Bilirubin 15 µmol/l ALP 52 u/l ALT 26 u/l γGT 58 u/l Albumin 40 g/l Serum corrected calcium 2.77 mmol/L Serum phosphate 0.90 mmol/l Parathyroid hormone 5.9 pmol/L normal range 1.2-5.8 pmol/L
A 24 hour urinary calcium test was performed based on the results above and revealed a result of 0.5 mmol/24 hours (normal range 2.4-7.4 mmol/24 hours)
What is the most likely diagnosis?
Primary hyperparathyroidism Secondary hyperparathyroidism Vitamin D toxicity Multiple endocrine neoplasia type A > Familial benign hypocalciuric hypercalcaemia
The most likely diagnosis in this scenario is familial benign hypocalciuric hypercalcaemia. Most cases are asymptomatic and blood test reveals hypercalcaemia with a reduced calcium urinary excretion rate (of under 0.02 mmol/L). There may also be normal to high parathyroid hormone, despite the elevated serum calcium levels.
Hyperparathyroidism Diagnosis - Example Question
A 60-year- old female presented with a six month history of polyuria, polydipsia and generalised aches and pains.
She is a known hypertensive for ten years and is taking bendroflumethiazide 2.5 mg daily. She has been taking calcium and vitamin D supplements for the last two years as she has a strong family history of osteoporosis.
On examination, her pulse rate is 80 beats per minute and her blood pressure is 150/90 mmHg. Cardiovascular, respiratory and abdominal examination were normal.
Investigations reveal:
Serum sodium 130 mmol/L Serum potassium 3.1 mmol/L Serum urea 7.7 mmol/L Serum creatinine 88 mol/L Serum corrected calcium 2.9 mmol/L Phosphate 0.8 mmol/L PTH 4.5 pmol/L (0.9-5.4) Urinalysis glycosuria ++
What is the most likely cause of this ladys symptoms?
> Primary hyperparathyroidism Vitamin D excess Bendroflumethizide induced hypercalcaemia Familial hypocalciuric hypercalcaemia Diabetes mellitus
This lady has hypercalcaemia which may be due to bendroflumethiazide or vitamin D excess, but the PTH level is inappropriately normal in the context of hypercalcaemia which indicates primary hyperparathyroidism rather than any other cause of hypercalcaemia in which the PTH would be suppressed by homeostatic mechanisms.
In addition, the phosphate level is low which is typical of primary hyperparathyroidism. The glycosuria is a distractor.
Primary Hyperthyroidism - Example Question
A 47-year-old woman is admitted to the surgical ward with severe loin to groin abdominal pain. A CT-KUB reveals a right-sided renal calculus. When you clerk her in she admits to you that she has not felt herself for the past few weeks with polyuria, polydipsia, constipation and altered mood.
Blood tests show:
Estimated glomerular filtration rate >60 ml/min
Adjusted calcium 3.1 mmol/l (2.1-2.6 mmol/l)
Phosphate 0.6 mmol/l (0.8-1.4 mol/l)
Parathyroid hormone 5.1 pmol/l (1.2-5.8 pmol/l)
Which of the following is the most likely cause for her symptoms?
> Primary hyperparathyroidism Secondary hyperparathyroidism Sarcoidosis Tertiary hyperparathyroidism Type 1 renal tubular acidosis
The most likely diagnosis here is primary hyperparathyroidism caused by parathyroid adenoma or hyperplasia. The classical biochemical findings are a high serum calcium and low phosphate. The parathyroid hormone level is either high or inappropriately normal.
Secondary hyperparathyroidism is caused by chronic hypocalcaemia (e.g. chronic kidney disease). Serum calcium is low or normal whilst parathyroid hormone levels are high.
Tertiary hyperparathyroidism develops from secondary hyperparathyroidism and results in autonomous parathyroid production. It is usually seen patients with end-stage renal disease.
Sarcoidosis and type 1 renal tubular acidosis are rare causes of hypercalcaemia.
Hypercalcaemia - Example Question
A 45-year-old lady is admitted to hospital with abdominal pain and malaise. She has no past medical history and takes no regular medications or supplements. Bloods tests show:
Ca 2++ 2.70 mmol/l
PO4 + 1.2 mmol/l
Creatinine 60 µmol/l
Chest X-ray - normal appearances
She denies taking any medications or supplements. Her chest X-ray is normal in appearance,and renal function normal. You ring the GP and find out her calcium was also slightly raised 8 years ago. What is the most likely diagnosis?
Secondary hyperparathyroidism Malignancy with bony metastasis Primary hyperparathyroidism > Familial hypocalciuric hypercalcaemia Sarcoidosis
PO4 would normally be low in primary hyperparathyroidism. Her renal function is normal excluding secondary hyperparathyroidism. Sarcoidosis is unlikely with a normal CXR. This leaves malignancy or familial hypocalciuric hypercalcaemia. Although malignancy is possible her raised Ca2+ 8 years makes familial hypocalciuric hypercalcaemia more likely.
Hypercalcaemia - Example Question
A 60-year-old man attends a medical health check-up at his GP surgery. He was fit and well with a past medical history of childhood asthma and osteoarthritis in his fingers. His observations were included a blood pressure of 129/80 mmHg, pulse of 82 bpm, and oxygen sats of 97%.
Blood tests were performed and revealed:
Hb 138 g/l Platelets 190 * 109/l WBC 7.6 * 109/l Na+ 139 mmol/l K+ 3.9 mmol/l Urea 4.1 mmol/l Creatinine 9.2 µmol/l Bilirubin 15 µmol/l ALP 52 u/l ALT 26 u/l γGT 58 u/l Albumin 40 g/l Serum corrected calcium 2.77 mmol/L Serum phosphate 0.90 mmol/l Parathyroid hormone 5.9 pmol/L normal range 1.2-5.8 pmol/L
A 24 hour urinary calcium test was performed based on the results above and revealed a result of 0.5 mmol/24 hours (normal range 2.4-7.4 mmol/24 hours)
What is the most likely diagnosis?
Primary hyperparathyroidism Secondary hyperparathyroidism Vitamin D toxicity Multiple endocrine neoplasia type A > Familial benign hypocalciuric hypercalcaemia
The most likely diagnosis in this scenario is familial benign hypocalciuric hypercalcaemia. Most cases are asymptomatic and blood test reveals hypercalcaemia with a reduced calcium urinary excretion rate (of under 0.02 mmol/L). There may also be normal to high parathyroid hormone, despite the elevated serum calcium levels.
Hypercalcaemia - Example Question
A 50-year-old female is referred to the clinic with hypercalcaemia found coincidentally during routine investigations. On further questioning she admits that she is taking a lot of antacid preparations (for her reflux oesophagitis) and calcium and vitamin D for protection against osteoporosis as her mother and sister have osteoporosis for which they are taking alendronate.
On examination there were no relevant findings.
Investigations reveal:
Serum sodium 135 mmol/L Serum potassium 3.5 mmol/L Serum urea 4.2 mmol/L Serum creatinine 77 mol/L Serum calcium 2.8 mmol/L Serum phosphate 0.8 mmol/L Plasma PTH 5.4 pmol/L (0.9-5.4) 24-h urinary calcium 1.5 mmol/24hr (2.5-7.5)
What is the most likely diagnosis?
Primary hyperparathyroidism Milk- alkali syndrome Hypervitaminosis D > Familial hypocalciuric hypercalcaemia Tertiary hyperparathyroidism
Familial hypocalciuric hypercalcaemia is an autosomal dominant disease characterized by asymptomatic hypercalcaemia with hypocalciuria and a normal PTH level. Most cases are discovered incidentally.
Parathyroid Hormone
PTH secreted by parathyroid glands
NET EFFECTS OF PTH:
- Increase in serum Ca2+
- Decrease in serum phosphate
1) PTH > causes decreased excretion of Ca2+ by the kidneys
> Increase in Calcium in the serum
2) PTH `> causes increase in rate of Ca2+ and phosphate absorption from bone (caused by PTH action on osteocytes)
3) PTH > causes increased excretion of phosphate by the kidneys > decreases serum phosphate
4) PTH > increases the calcium and phosphate absorption from the gut
Differentiating between Primary, Secondary and Tertiary Hyperparathyroidism
Hyperparathyroidism (HPT) results when there is excessive secretion of parathyroid hormone (PTH).PTH is secreted by the four parathyroid glands, located in the neck behind the thyroid gland. It regulates serum calcium and phosphate levels and also plays a part in bone metabolism. High levels of PTH cause serum calcium levels to increase and serum phosphate levels to fall.
HPT may be:
Primary - one parathyroid gland (or more) produces excess PTH. This may be asymptomatic.
Secondary - there is increased secretion of PTH in response to low calcium because of kidney, liver, or bowel disease.
Tertiary - there is autonomous secretion of PTH, usually because of chronic kidney disease (CKD).
