Medicine – Causes of Hypoparathyroidism

Hypoparathyroidism is an endocrine disorder characterised by deficient secretion or action of parathyroid hormone (PTH). Because PTH is one of the major regulators of calcium and phosphate balance, deficiency of PTH produces the characteristic biochemical combination of:

↓ PTH + ↓ Ca²⁺ + ↑ phosphate.

The major causes include surgical removal or damage to the parathyroid glands, autoimmune destruction, congenital absence or abnormal development of the glands, and genetic disorders affecting PTH production or action.

An important correction to the original notes is that pseudohypoparathyroidism is not true hypoparathyroidism. In pseudohypoparathyroidism, PTH is produced but the target tissues are resistant to its action, so PTH is elevated rather than decreased.

1. Normal Function of PTH

PTH is secreted by the:

Parathyroid glands.

Its secretion is primarily regulated by the concentration of:

Ionised calcium in the blood.

When serum calcium falls:

↓ Ca²⁺

↓

Parathyroid calcium-sensing receptors detect the fall

↓

↑ PTH secretion

↓

Serum calcium is restored toward normal.

2. Major Actions of PTH

PTH acts mainly on:

Bone

and

Kidney.

It also indirectly increases intestinal calcium absorption through activation of:

Vitamin D.

The overall effect is:

↑ Serum calcium

and

↓ Serum phosphate.

Therefore PTH can be remembered as a hormone that:

RAISES CALCIUM AND LOWERS PHOSPHATE.

3. PTH and the Kidney

In the kidney, PTH increases:

Calcium reabsorption, particularly in the distal nephron.

At the same time, PTH decreases:

Phosphate reabsorption in the proximal tubule.

Therefore:

↑ PTH → ↑ urinary phosphate excretion – phosphaturia.

PTH also stimulates renal:

1α-hydroxylase

which converts:

25-hydroxyvitamin D

into:

1,25-dihydroxyvitamin D – calcitriol.

4. PTH and Vitamin D

Calcitriol increases intestinal absorption of:

Calcium

and

Phosphate.

Therefore PTH indirectly supports serum calcium by increasing:

Calcitriol production → intestinal calcium absorption.

When PTH is deficient:

↓ Calcitriol production

contributes to:

Hypocalcaemia.

5. What Happens in Hypoparathyroidism?

When PTH secretion is inadequate:

↓ PTH

↓

↓ Renal calcium reabsorption

• ●

↓ Calcitriol production

↓

↓ Intestinal calcium absorption

↓

Hypocalcaemia.

At the same time:

↓ PTH

↓

Loss of the normal phosphaturic effect

↓

↑ Renal phosphate reabsorption

↓

Hyperphosphataemia.

Therefore the classic biochemical pattern is:

Ca²⁺ ↓

Phosphate ↑

PTH ↓ or inappropriately low.

6. Surgical Hypoparathyroidism

The original notes correctly identify:

Parathyroidectomy

as an important cause.

Hypoparathyroidism can occur when the parathyroid glands are:

Intentionally removed

or

Accidentally damaged, removed or devascularised during neck surgery.

This is one of the most important acquired causes of hypoparathyroidism.

7. Thyroid Surgery

Because the parathyroid glands lie closely related to the posterior surface of the thyroid gland, they may be injured during:

Thyroidectomy.

Possible mechanisms include:

Accidental removal.

Damage to the parathyroid blood supply.

Direct surgical injury.

This can produce postoperative:

Hypocalcaemia.

8. Temporary Versus Permanent Postoperative Hypoparathyroidism

After thyroid or parathyroid surgery, hypoparathyroidism may be:

Temporary

or

Permanent.

Temporary hypocalcaemia can occur because the remaining glands are transiently dysfunctional or their blood supply has been disturbed.

Permanent disease occurs when insufficient functioning parathyroid tissue remains.

Therefore calcium should be monitored carefully following relevant:

Neck surgery.

9. Intentional Parathyroidectomy

Parathyroid tissue may intentionally be removed during treatment of severe:

Primary hyperparathyroidism

or selected cases of severe:

Secondary or tertiary hyperparathyroidism.

Excessive removal can result in:

Hypoparathyroidism and hypocalcaemia.

10. Hungry Bone Syndrome – Important Distinction

Hypocalcaemia after parathyroid surgery does not always mean permanent hypoparathyroidism.

After removal of a source of severe PTH excess, previously high-turnover bone may rapidly take up:

Calcium, phosphate and magnesium.

This is called:

Hungry bone syndrome.

It can produce prolonged postoperative hypocalcaemia.

Therefore:

POST-PARATHYROIDECTOMY HYPOCALCAEMIA

may reflect either:

Low PTH

or

Hungry bone syndrome.

The biochemical patterns help distinguish them.

11. Autoimmune Hypoparathyroidism

The original notes correctly include:

Autoimmune disease.

The immune system can destroy or impair the:

Parathyroid glands.

This produces:

Reduced PTH secretion.

Autoimmune hypoparathyroidism may occur in isolation or as part of a broader:

Autoimmune polyglandular syndrome.

12. Autoimmune Polyglandular Syndrome Type 1

A classic association is:

Autoimmune polyendocrine syndrome type 1 – APS-1, also called APECED.

It is associated with mutations in:

AIRE.

The classic manifestations include:

Chronic mucocutaneous candidiasis.

Hypoparathyroidism.

Primary adrenal insufficiency – Addison disease.

Therefore hypocalcaemia in a patient with other autoimmune endocrine abnormalities should raise consideration of:

Autoimmune hypoparathyroidism.

13. DiGeorge Syndrome

The original notes correctly identify:

DiGeorge syndrome.

DiGeorge syndrome is usually related to:

22q11.2 deletion.

There is abnormal development of structures derived primarily from the:

Third and fourth pharyngeal pouches.

This can lead to abnormal development or absence of:

Parathyroid tissue

and the:

Thymus.

14. Hypocalcaemia in DiGeorge Syndrome

Because parathyroid development is impaired:

↓ Parathyroid tissue

↓

↓ PTH

↓

Hypocalcaemia.

Affected infants may therefore present with:

Tetany

or

Seizures due to hypocalcaemia.

15. Other Features of DiGeorge Syndrome

The phenotype is variable, but important associations include:

Congenital heart disease, particularly conotruncal abnormalities.

Thymic hypoplasia or aplasia with T-cell immune dysfunction.

Characteristic craniofacial/palatal abnormalities.

Hypoparathyroidism with hypocalcaemia.

Therefore a useful association is:

CARDIAC DEFECT + IMMUNE DEFICIENCY + HYPOCALCAEMIA → THINK 22q11.2 DELETION/DIGEORGE SYNDROME.

16. Pseudohypoparathyroidism – Important Correction

The original notes list:

“Receptor defect – pseudohyperparathyroidism.”

The correct term is:

Pseudohypoparathyroidism.

More importantly, pseudohypoparathyroidism is not a cause of true PTH deficiency.

Instead, the body produces PTH, but target tissues have:

Resistance to PTH action.

17. Pseudohypoparathyroidism Mechanism

Because the kidneys do not respond appropriately to PTH:

Renal calcium-conserving/PTH-dependent effects are impaired

and

Phosphate excretion is reduced.

Therefore:

Calcium ↓

Phosphate ↑.

The parathyroid glands detect the low calcium and respond by secreting more PTH.

Therefore:

PTH ↑.

18. Hypoparathyroidism Versus Pseudohypoparathyroidism

This is an extremely important examination distinction.

TRUE HYPOPARATHYROIDISM:

PTH:

↓

Calcium:

↓

Phosphate:

↑

PSEUDOHYPOPARATHYROIDISM:

PTH:

↑

Calcium:

↓

Phosphate:

↑

The difference is therefore:

LOW PTH → true hypoparathyroidism.

HIGH PTH → PTH resistance/pseudohypoparathyroidism, assuming the biochemical and clinical context fits.

19. Albright Hereditary Osteodystrophy

Some forms of pseudohypoparathyroidism are associated with physical features collectively known as:

Albright hereditary osteodystrophy – AHO.

Features can include:

Short stature.

Round face.

Brachydactyly, particularly shortening of selected metacarpals/metatarsals.

Subcutaneous ossification.

The phenotype and hormone resistance depend on the underlying molecular subtype.

20. Genetic Causes of True Hypoparathyroidism

Several inherited disorders can cause genuine:

PTH deficiency.

These may affect:

Parathyroid development

or

PTH synthesis/secretion.

Although individually uncommon, they are particularly important when hypoparathyroidism presents in:

Childhood

or when there is a strong:

Family history.

21. Activating Calcium-Sensing Receptor Disorders

The:

Calcium-sensing receptor – CaSR

helps parathyroid cells determine whether serum calcium is sufficiently high.

Certain activating genetic abnormalities can make the receptor behave as though calcium is higher than it actually is.

Therefore PTH secretion becomes:

Inappropriately suppressed.

This can cause:

Hypocalcaemia with low or inappropriately normal PTH.

Renal calcium loss may also be increased.

22. Severe Hypomagnesaemia – Important Additional Cause

An important cause not included in the original list is:

Severe hypomagnesaemia.

Magnesium is necessary for normal:

PTH secretion

and

PTH action.

Therefore severe magnesium deficiency can cause:

Reduced PTH secretion

and

Peripheral PTH resistance.

23. Magnesium and Refractory Hypocalcaemia

This produces an important clinical pattern:

Hypomagnesaemia

↓

↓ PTH secretion/action

↓

Hypocalcaemia.

Therefore:

HYPOCALCAEMIA THAT DOES NOT CORRECT APPROPRIATELY → CHECK MAGNESIUM.

Calcium may remain difficult to correct until:

Magnesium is replaced.

24. Infiltrative and Destructive Disorders

Rarely, parathyroid tissue can be damaged by infiltrative or destructive processes.

Examples can include:

Iron overload, such as severe haemochromatosis or transfusional iron overload.

Copper deposition in selected circumstances.

Metastatic/infiltrative disease.

These are much less common than:

Surgery or autoimmune disease.

25. Clinical Features

Most symptoms of hypoparathyroidism result from:

Hypocalcaemia.

Low extracellular calcium increases:

Neuromuscular excitability.

Therefore patients can develop:

Perioral tingling.

Paraesthesia.

Muscle cramps.

Carpopedal spasm.

Tetany.

26. Chvostek Sign

Chvostek sign refers to contraction of facial muscles following tapping over the facial nerve.

It may occur with:

Hypocalcaemia.

However, it is not perfectly sensitive or specific and may occasionally be present in people without clinically important hypocalcaemia.

27. Trousseau Sign

Trousseau sign is carpal spasm precipitated by inflation of a blood-pressure cuff above systolic pressure for several minutes.

It reflects increased:

Neuromuscular excitability due to hypocalcaemia.

It is generally a more useful sign of latent tetany than Chvostek sign.

28. Severe Hypocalcaemia

Severe hypocalcaemia can produce:

Tetany.

Laryngospasm.

Bronchospasm.

Seizures.

Altered mental status.

Cardiac electrical abnormalities may also occur.

29. ECG Changes

Hypocalcaemia classically causes:

QT-interval prolongation.

Severe electrolyte disturbance can increase the risk of:

Cardiac arrhythmias.

Therefore symptomatic or severe hypocalcaemia requires prompt assessment and treatment.

30. Chronic Hypoparathyroidism

Longstanding hypoparathyroidism may be associated with:

Cataracts.

Dental abnormalities, particularly when disease begins during development.

Basal ganglia and other intracranial calcification.

Neuropsychiatric symptoms.

Chronic management must also avoid excessive calcium replacement because of the risk of:

Hypercalciuria and renal complications.

31. Diagnosis

The original notes correctly state that true hypoparathyroidism produces:

↓ Calcium

and

↓ PTH.

However, phosphate is also extremely important.

The characteristic pattern is:

Calcium ↓

Phosphate ↑

PTH ↓ or inappropriately normal.

32. Why “Inappropriately Normal” PTH Matters

When calcium is low, normal physiology should produce:

A substantial rise in PTH.

Therefore a PTH concentration that lies technically within the laboratory reference range may still be:

Inappropriately normal.

In a patient with hypocalcaemia, PTH should be elevated.

Thus:

LOW Ca²⁺ + PTH that fails to rise appropriately → suspect hypoparathyroidism.

33. Confirming True Hypocalcaemia

Total serum calcium is affected by:

Albumin concentration.

Therefore calcium assessment may require consideration of:

Albumin-adjusted calcium

or direct measurement of:

Ionised calcium, particularly in selected acute or complex situations.

A low total calcium caused simply by hypoalbuminaemia is not equivalent to true:

Ionised hypocalcaemia.

34. Other Investigations

Evaluation commonly includes:

Calcium.

Phosphate.

PTH.

Magnesium.

Renal function.

25-hydroxyvitamin D.

Depending on the context, urinary calcium and additional genetic or autoimmune investigations may be appropriate.

35. Treatment Principles

Treatment aims to:

Relieve symptomatic hypocalcaemia

while maintaining calcium at a safe level and avoiding excessive:

Urinary calcium excretion.

Management depends on whether hypocalcaemia is:

Acute/severe

or

Chronic.

36. Acute Symptomatic Hypocalcaemia

Severe symptomatic hypocalcaemia may require:

Intravenous calcium, commonly calcium gluconate, with appropriate monitoring.

This is particularly relevant with:

Tetany.

Seizures.

Laryngospasm.

Significant ECG abnormalities.

The underlying cause must simultaneously be addressed.

37. Chronic Hypoparathyroidism

Long-term conventional treatment commonly uses:

Oral calcium

plus:

Active vitamin D, such as calcitriol or an appropriate analogue.

Why active vitamin D?

Because low PTH reduces renal activation of vitamin D.

Therefore providing active vitamin D helps increase:

Intestinal calcium absorption.

38. Correct Magnesium

If magnesium is deficient:

Magnesium must be corrected.

Otherwise PTH secretion and action may remain impaired and the hypocalcaemia may be:

Refractory to calcium treatment.

Therefore:

LOW Ca²⁺ + LOW Mg²⁺ → CORRECT Mg²⁺.

39. Monitoring Chronic Treatment

The objective is not necessarily to push serum calcium to the high-normal range.

Excessive calcium and active vitamin D treatment can produce:

Hypercalciuria.

This can contribute to:

Nephrolithiasis.

Nephrocalcinosis.

Renal impairment.

Therefore serum and urinary calcium require appropriate monitoring during chronic treatment.

40. Causes of Hypoparathyroidism – Note Form

POSTSURGICAL:

Parathyroidectomy.

Accidental parathyroid removal during thyroid surgery.

Parathyroid vascular injury during neck surgery.

AUTOIMMUNE:

Isolated autoimmune hypoparathyroidism.

Autoimmune polyendocrine syndrome type 1 – APECED.

CONGENITAL/GENETIC:

DiGeorge syndrome – 22q11.2 deletion.

Genetic abnormalities of parathyroid development or PTH secretion.

Activating calcium-sensing receptor disorders.

FUNCTIONAL PTH DEFICIENCY:

Severe hypomagnesaemia.

RARE DESTRUCTIVE/INFILTRATIVE CAUSES:

Iron overload and other infiltrative disorders.

41. Pseudohypoparathyroidism – Keep Separate

The original notes place pseudohypoparathyroidism under causes of hypoparathyroidism.

For examination purposes, it is better to keep it separate because:

The parathyroid glands are producing PTH.

The problem is:

Target-organ resistance to PTH.

Therefore:

Ca²⁺ ↓

PO₄³⁻ ↑

but:

PTH ↑.

42. Biochemical Patterns – Note Form

TRUE HYPOPARATHYROIDISM

Calcium:

↓

Phosphate:

↑

PTH:

↓ or inappropriately normal

PSEUDOHYPOPARATHYROIDISM

Calcium:

↓

Phosphate:

↑

PTH:

↑

PRIMARY HYPERPARATHYROIDISM

Calcium:

↑

Phosphate:

↓ or low-normal

PTH:

↑ or inappropriately normal

SECONDARY HYPERPARATHYROIDISM DUE TO VITAMIN D DEFICIENCY

Calcium:

↓ or low-normal

Phosphate:

↓

PTH:

↑

ALP:

↑

SECONDARY HYPERPARATHYROIDISM DUE TO ADVANCED CKD

Calcium:

↓ or normal

Phosphate:

↑

PTH:

↑

43. Important Corrections to the Original Notes

The original:

“Parathyroidectomy – intentional or accidental”

is correct.

Surgery is one of the most important acquired causes of true hypoparathyroidism.

The original:

“Autoimmune”

is also correct.

Remember the association with:

APS-1/APECED → candidiasis + hypoparathyroidism + Addison disease.

The original:

“DiGeorge syndrome”

is correct.

Remember:

22q11.2 deletion → abnormal parathyroid development → ↓ PTH → hypocalcaemia.

The original term:

“pseudo-hyperparathyroidism”

should be corrected to:

PSEUDOHYPOPARATHYROIDISM.

This is PTH resistance, not PTH deficiency.

Therefore:

PTH is HIGH, not low.

The original diagnosis:

↓ Ca²⁺ + ↓ PTH

is correct for true hypoparathyroidism, but add:

↑ PHOSPHATE.

Therefore the complete classic pattern is:

↓ Ca²⁺ + ↑ PO₄³⁻ + ↓ PTH.

Key Clinical Pattern

For rapid recall:

PTH RAISES CALCIUM AND LOWERS PHOSPHATE.

Therefore if PTH disappears:

↓ PTH

↓

↓ Ca²⁺

• ●

↑ PO₄³⁻.

The major causes are:

NECK/PARATHYROID SURGERY + AUTOIMMUNE DESTRUCTION + DiGEORGE/CONGENITAL DISEASE + SEVERE HYPOMAGNESAEMIA.

The most important distinction is:

TRUE HYPOPARATHYROIDISM

Ca ↓ | PO₄ ↑ | PTH ↓

versus:

PSEUDOHYPOPARATHYROIDISM

Ca ↓ | PO₄ ↑ | PTH ↑.

And the classic symptomatic presentation is:

HYPOCALCAEMIA → PERIORAL TINGLING + PARAESTHESIA + CRAMPS + CARPOPEDAL SPASM + TETANY ± SEIZURES, with possible:

PROLONGED QT INTERVAL.