Hyperparathyroidism, Parathyroid Hormone and Calcium Flashcards
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.
