The document discusses calcium homeostasis and disorders of calcium and phosphate metabolism. It provides details on: 1. The functions of parathyroid hormone (PTH) and how it regulates calcium levels. 2. Causes of hypocalcemia including hypoparathyroidism and vitamin D deficiency. 3. Causes of hypercalcemia including primary hyperparathyroidism and malignant diseases. 4. How laboratory tests can help diagnose disorders like hypocalcemia and hyperparathyroidism.

1. www.gmu.ac.ae COLLEGE OF MEDICINE
October 9, 2023
Laboratory investigations of Parathyroid gland &
disorders of mineral metabolism
MBBS
Endocrine System & Breast 210
Dr. Dalia A.Gaber
Associate Professor of Medical Biochemistry & Molecular Biology
FAIMER Fellow

2. Lecture’s Objectives
• Identify the functions of the hormone secreted by the parathyroid gland; PTH.
•Explain the normal plasma calcium level & its main functions in the body.
•Discuss causes of hypocalcemia & hypercalcemia.
•Interpret lab investigations of calcium & phosphate disorders.

3. A 56-year-old woman was admitted to hospital for cataract extraction. She
was in good health apart from her failing vision. She had undergone
thyroidectomy for a multinodular goiter (enlarged thyroid) 20 years earlier.
Both Chvostek and Trousseau signs were positive.
Serum: calcium 7 mg/dL (N. 9-11 mg/dL)
phosphate 5.2 mg/dL (N. 2.8-4.5 mg/dL)
creatinine 1.0 mg/dL (N. 0.6-1.1 mg/dL)
eGFR 100 mL/min/1.73 m
2
alkaline phosphatase 76 U/L (N. 44-147 U/L)
Plasma: PTH <1 pmol/L (N. 10-55pmol/L )
Case presentation
Interpret the lab test results.

4. Distribution of calcium in human plasma. Some 80% of the amount bound to protein is
bound to albumin, and the remainder to γ-globulins.
Plasma calcium 9-11 mg/dL
Ionized

5. Hypocalcemia
• Deficiency or impaired metabolism of vitamin D, CKD, hypoparathyroidism
and hypomagnesaemia account for the majority of cases.
• A low plasma calcium concentration is always interpreted in relation to the
albumin concentration (albumin transports calcium in blood).
• The clinical features are increased neural and muscular excitability.
Disorders of Calcium & Phosphate metabolism

6. • Early signs of hypocalcemia include: Chvostek sign (contraction of facial
muscles on tapping facial nerve) and Trousseau sign (carpal spasm when
sphygmomanometer cuff applied to upper arm is inflated to midway between
systolic and diastolic blood pressures for 3 min) may be positive before other
signs are present (latent tetany).
• Mild hypocalcemia may be asymptomatic; in severe cases, the condition can be
life-threatening.

7. Vitamin D deficiency
• Vitamin D deficiency, which causes osteomalacia in adults and rickets in
children.
• Deficiency may be caused by inadequate endogenous synthesis or dietary
supply of vitamin D, or malabsorption.
• There is decreased absorption of calcium and phosphate from the gut.
Causes of hypocalcemia

8. • Vitamin D deficiency is a cause of secondary hyperparathyroidism.
• This further lowers the plasma phosphate concentration, and patients with vitamin D
deficiency often have hypophosphatemia.
• Plasma alkaline phosphatase activity increases and hypocalcemia may develop.
• The plasma concentration of 25-hydroxycholecalciferol is low.

9. • Total plasma calcium
• Ionized calcium can be measured using an ion-selective electrode (usually part of
a blood gas analyzer).
Accurate measurements of ionized calcium require the exclusion of air from the
sample to avoid changes in binding of calcium to albumin in response to changes in
hydrogen ion concentration (pH).
Lab diagnosis of hypocalcemia

10. A 56-year-old woman was admitted to hospital for cataract extraction. She
was in good health apart from her failing vision. She had undergone
thyroidectomy for a multinodular goiter (enlarged thyroid) 20 years earlier.
Both Chvostek and Trousseau signs were positive.
Serum: calcium 7 mg/dL (N. 9-11 mg/dL)
phosphate 5.2 mg/dL (N. 2.8-4.5 mg/dL)
creatinine 1.0 mg/dL (N. 0.6-1.1 mg/dL)
eGFR 100 mL/min/1.73 m
2
alkaline phosphatase 76 U/L (N. 44-147 U/L)
Plasma: PTH <1 pmol/L (N. 10-55pmol/L )
Back to the first case……………
Interpret the lab test results.

11. Summary
Asymptomatic severe hypocalcemia and hyperphosphatemia with normal kidney
function and low PTH.
Interpretation
The combination of hypocalcemia, hyperphosphatemia, normal alkaline
phosphatase and low PTH is typical of hypoparathyroidism. In most other
conditions causing hypocalcemia (apart from hypomagnesaemia), PTH
secretion is increased.
Discussion
Chronic hypocalcemia from hypoparathyroidism (in this case probably caused by
surgical damage to the parathyroid glands) is often asymptomatic and may go
undetected for many years. Cataracts are a recognized complication. Patients
should be monitored long term after major thyroid or other neck surgery because
hypocalcemia can develop many years later.

12. Secondary hyperparathyroidism
• Plasma PTH concentrations are also raised in many patients with chronic kidney
disease (CKD) and with vitamin D deficiency.
• Both these conditions are associated with decreased synthesis of calcitriol, which
causes hypocalcemia, and the increase in PTH secretion is an appropriate
physiological response.
• This is termed secondary hyperparathyroidism .
• The increase in PTH may not normalize the plasma calcium.

13. • Two conditions account for up to 90% of cases: primary hyperparathyroidism and
malignancy.
• It may be discovered during the investigation of an illness known to cause
hypercalcemia.
• However, it is often clinically silent and discovered incidentally when calcium
concentration is measured for other reasons.
Disorders of Calcium & Phosphate metabolism
Hypercalcemia

14. 1. Malignant disease
• Malignant disease is a common cause of hypercalcemia, particularly in patients
in hospital.
• There may or may not be obvious metastases in bone.
• Patients with hypercalcemia and malignant disease are usually symptomatic.
• It occurs in solid tumors, due to the secretion by the tumor of PTH-related
peptide.
Causes of hypercalcemia

15. • Primary hyperparathyroidism can occur at any age but is most common in
postmenopausal women.
• It is usually due to a parathyroid adenoma, less often to diffuse hyperplasia of
the glands, and only rarely to parathyroid carcinoma.
• The definitive treatment for hyperparathyroidism is surgical removal of the
affected glands.
• Patients with mild asymptomatic hypercalcemia are at increased risk of
development of osteoporosis and renal impairment, and should be reassessed
regularly.
2. Primary hyperparathyroidism

16. • A high fluid intake should be maintained to discourage renal calculus formation.
• Vitamin D should be given if the patient is deficient.
• There is hypercalciuria with increased risk of stone formation, the estimated
glomerular filtration rate (eGFR) is <60 mL/min/1.73 m 2 or in patients younger
than 50 years.

17. 3. Patients with kidney failure become hypercalcemic, caused by the development
of autonomous PTH secretion, as a result of the prolonged hypocalcemic stimulus.
• Hypercalcemia is sometimes seen in patients with 4. thyrotoxicosis , although
thyroid hormones have no specific role in calcium homoeostasis. Thyrotoxicosis
can also cause osteoporosis.
• 5. Excessive intake of vitamin D itself is a rare cause of hypercalcemia
Causes of hypercalcemia

18. Lab Investigation of hypercalcemia
• The plasma phosphate concentration is of limited diagnostic value: although low
in most uncomplicated cases of primary hyperparathyroidism, it can also be
decreased in hypercalcemia caused by malignancy, and can be raised in either
condition if there is renal impairment.
• Plasma alkaline phosphatase activity can be elevated in either condition,
although it is more frequently so in malignant disease.
• Measurement of PTH, using an assay for the intact hormone, is essential.
• The measurement of urinary calcium/creatinine clearance ratio will help
• Serum protein electrophoresis and measurement of light chains in urine and
serum are required if multiple myeloma is suspected.

19. Wrap-up Summary
• Calcium has many functions in the body in addition to its structural role in bones
and teeth. It is essential for muscle contraction , affects the excitability of
nerves , is a second messenger , involved in the action of several hormones, and
is required for blood coagulation.
• About half the calcium in the plasma is bound to protein ; it is the unbound fraction
that is physiologically active and whose concentration is closely regulated.
• Two hormones have a central role in calcium homoeostasis. The main action
of calcitriol , the hormone derived from vitamin D by successive hydroxylations in the
liver and kidneys, is to stimulate calcium (and phosphate) uptake from the gut.
• Parathyroid hormone (PTH) , secreted in response to a fall in plasma ionized
calcium concentration, stimulates calcitriol formation, stimulates calcium resorption
from bone and reabsorption by the renal tubules, and has a powerful phosphaturic
action.

20. • These two hormones, along with fibroblast growth factor 23 , also regulate
extracellular phosphate concentration. Calcitonin has only a minor role in calcium
homoeostasis.
• The common causes of hypercalcemia are primary hyperparathyroidism , caused
by parathyroid adenomas or hyperplasia, and malignant disease (including
myeloma), with or without metastasis to bone. Less common causes include
sarcoidosis, thyrotoxicosis and overdosage with vitamin D or its derivatives.
• Mild hypercalcaemia is often asymptomatic; when more severe, clinical features
may include bone and abdominal pain, kidney stones, polyuria, thirst and
behavioural disturbances.
• Hypocalcaemia causes hyperexcitability of nerve and muscle, leading to muscle
spasm (tetany) and, in severe cases, to convulsions. Causes include vitamin D
deficiency and hypoparathyroidism.

21. • Vitamin D deficiency may be either dietary in origin, often exacerbated by little
exposure to sunlight (and hence reduced endogenous synthesis), or caused by
malabsorption.
• Hyperphosphatemia is particularly associated with renal impairment; it inhibits
vitamin D metabolism and can cause hypocalcemia.
• Severe hypophosphatemia , such as can occur with inadequate phosphate
provision during intravenous feeding, has potentially harmful effects on many body
tissues, particularly blood cells and skeletal muscle.

22. Question
A 40-year old man was diagnosed with parathyroid adenoma. His estimated
glomerular filtration rate was 55 mL/min/1.73 m 2. What is the interpretation &
the cause of this eGFR value?
a. High PTH directly damages the renal tubules
b. Hypercalcuria which leads to renal impairment
c. Hyperphosphatemia with normal eGFR
d. Vitamin D deficiency leading to renal dysfunction

23. ANSWER: B

24. References
• Henry's Clinical Diagnosis and Management by Laboratory Methods, Twenty Fourth Edition, Elsevier 2022.
• Marshall, William J, Day, Andrew,Lapsley, Marta, Clinical Chemistry, ninth Edition Elsevier 2021