Hypoparathyroidism

Table of contents
Key points ⚡
Succinct notes to superpower your revision
Hypoparathyroidism\: endocrine disorder characterised by low calcium, high phosphate, and low or inappropriately normal
PTH.
Pathophysiology\: low PTH leads to impaired calcium regulation (bone resorption, renal reabsorption, and GI absorption),
causing hypocalcaemia and hyperphosphataemia.
Causes\: most common is neck surgery (iatrogenic); other causes include genetic disorders (e.g. DiGeorge syndrome, APS-
1), in
Risk factors\: recent neck surgery, chronic alcohol use, malabsorption, haemochromatosis, Wilson's disease, genetic
syndromes (e.g. DiGeorge).
Symptoms\: paraesthesia, muscle cramps, carpopedal spasm, tetany, seizures, stridor (due to laryngospasm).
Signs\: positive Chvostek’s and Trousseau’s signs, dental abnormalities, dry skin, brittle nails.
Investigations\: low calcium, low/normal PTH, high phosphate, low vitamin D, prolonged QT on ECG, renal ultrasound (renal
calculi).
Management\: acute\: IV calcium gluconate for severe hypocalcaemia; chronic\: vitamin D analogues (calcitriol, alfacalcidol),
calcium supplements; PTH replacement in refractory cases.
Complications\: cardiac arrhythmias, chronic kidney disease, renal calculi, cataracts, seizures, basal ganglia calci
Article 🔍
A comprehensive topic overview

Introduction

Hypoparathyroidism is an endocrine disorder characterised by low serum calcium, raised serum phosphate and low,
undetectable, or inappropriately normal parathyroid hormone (PTH) levels in the blood.
1
It is a rare condition, with an estimated incidence ranging from 0.8 to 2.3 per 100,000 person-years, and a prevalence
ranging between 6.4 to 37 per 100,000.
2-3

Aetiology

Pathophysiology
In normal physiology, the parathyroid glands secrete PTH in response to hypocalcaemia. PTH acts on the bones, kidneys,
and gastrointestinal (GI) tract to raise serum calcium. In hypoparathyroidism, PTH levels are low, meaning that the serum
calcium cannot be adequately raised via bone resorption and renal tubular calcium reabsorption.
The kidneys are also unable to adequately facilitate the vitamin D-mediated absorption of calcium by the GI tract through
increased synthesis of the active form of vitamin D (1,25-dihydroxyvitamin D). 4
Therefore, 1,25-dihydroxyvitamin D levels are
usually low.
Serum phosphate levels rise due to decreased phosphate excretion by the kidney in the presence of low PTH.
5
Causes of hypoparathyroidismThere are several di
congenital/genetic causes. The most common cause of hypoparathyroidism is iatrogenic, following neck surgery.
6
Acquired causes
Neck surgery is by far the most common cause, accounting for around 75% of cases in adults. 3
the parathyroid glands include\:
4-5
Surgeries that may involve
Accidental damage to, or removal of, the parathyroid glands during anterior neck surgery (typically thyroid surgery)
Planned removal of the parathyroid glands as part of the management of hyperparathyroidism
Other acquired causes include in
copper deposition in Wilson’s disease, and radiation (e.g. neck irradiation in radiotherapy treatment). Acquired
hypoparathyroidism can also be functional, secondary to either hypermagnesaemia or severe hypomagnesaemia.
Hypoparathyroidism can be transient due to excess alcohol, burns or severe acute illness. Isolated idiopathic
hypoparathyroidism has also been described, with no clear aetiology identi
1, 4
Congenital/genetic causes
Genetic causes of hypoparathyroidism are numerous and are rarer than acquired causes. These can present as isolated
hypoparathyroidism or as part of a syndrome. 1
DiGeorge syndrome is the most common genetic cause and is
characterised by hypoparathyroidism, abnormal facies, cardiac malformations and thymus underdevelopment.
4
Other notable genetic causes include\:
Autoimmune polyendocrine syndrome type 1 (APS-1)\: an autoimmune, autosomal recessive disorder. The three major
clinical features are chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insu
1
Hypoparathyroidism, deafness and renal (HDR) dysplasia genetic syndrome
4
Some newborns may also experience transient hypoparathyroidism in the neonatal period. Newborns will undergo a
reduction in their serum calcium in the
PTH surge, but in some cases (e.g. preterm births, maternal diabetes), a reduction or delay in PTH release can cause
hypocalcaemia.
5
Pseudohypoparathyroidism
This is a rare inherited disorder with target organ resistance to PTH, resulting in low serum calcium and high
phosphate, with a high PTH.
Patients with the commonest form of pseudohypoparathyroidism (type 1a) have a characteristic pattern of skeletal
abnormalities, known as Albright’s hereditary osteodystrophy. These physical abnormalities include short stature,
round face, obesity and short metacarpals.
7-8

Risk factors

Risk factors for developing hypoparathyroidism typically include characteristics related to the various aetiologies\:
3, 5
Recent anterior neck surgery
Chronic alcohol excess (hypomagnesaemia)
Chronic malabsorption (hypomagnesaemia)
Proton pump inhibitors (hypomagnesaemia)
Frequent blood transfusions e.g. in thalassaemia (iron deposition)
Hereditary haemochromatosis (iron deposition)
Wilson's disease (copper deposition)
Genetic syndromes discussed above
Metastatic cancerClinical features
The clinical features result from increased neuromuscular excitability due to hypocalcaemia. Patients may also be
asymptomatic.
History
Typical symptoms include\:
5, 7-8
Paraesthesia (tingling and/or numbness)\: especially of
Muscle pains and cramps
Carpopedal spasm
Stridor due to laryngospasm
Tetany
Seizures
Other important areas to cover in the history include\:
Past surgical history\: any recent or previous surgery to the neck area
Family history of hypoparathyroidism or other endocrine disorders
Clinical examination
Typical clinical
5-7
Chvostek’s sign\: elicited by tapping on the facial nerve in front of the ear. Twitching of the corner of the mouth indicates a
positive result. This is not speci
Trousseau’s sign\: elicited by occluding the blood supply to the arm by in
arterial pressure for 3 minutes. Carpopedal spasm is induced in a positive result.
Clinical signs associated with relevant clinical syndromes\: e.g. abnormal facies in DiGeorge syndrome, chronic
mucocutaneous candidiasis in APS-1, generalised bronzing and signs of liver disease in haemochromatosis.
Dental abnormalities and enamel dysplasia
Dry skin and brittle nails
Ensure to examine the neck for scars that may suggest postsurgical hypoparathyroidism.
6

Di

Important di
5
Hypomagnesaemia\: serum calcium may be normal, symptoms will typically be out of proportion to the degree of
hypocalcaemia
Hypoalbuminaemia\: likely to be asymptomatic, albumin-corrected serum calcium would be normal
Chronic kidney disease (CKD)\: other signs of CKD likely to be present e.g. reduced urine output or pruritus
Vitamin D de
Pseudohypoparathyroidism\: PTH levels will be elevated

Investigations

Bedside investigations
Relevant bedside investigations include\:
5
ECG\: prolonged QT interval may be present with hypocalcaemia, which may progress to life-threatening arrhythmias
such as ventricular
If a patient is acutely unwell with severe hypoparathyroidism, then a set of baseline observations should be taken as part of
an ABCDE assessment.
Laboratory investigationsRelevant laboratory investigations include\:Serum PTH
Corrected serum calcium
Phosphate
Vitamin D
Urea and electrolytes
Magnesium
Low or inappropriately normal PTH in the setting of hypocalcaemia distinguishes the disease from secondary causes of
hypocalcaemia, in which PTH is elevated.
1, 4
Imaging
The following imaging investigations can be considered\:
Renal ultrasound\: for renal calculi due to increased calcium excretion in urine, which may occur when attempting to
correct hypocalcaemia
Hand X-ray\: for shortened metacarpals
MRI brain\: for basal ganglia calci
Echocardiogram\: to assess cardiac abnormalities (in DiGeorge syndrome)
Other investigations
Genetic studies can be considered if family or personal history suggests a potential genetic cause.
4-5

Management

Acute management
In the acute phase, correcting the hypocalcaemia is the priority, as it can occur rapidly following neck surgery.
7
In severe hypocalcaemia (calcium \< 1.9 mmol/L or symptomatic at any level below reference range),
of 10% calcium gluconate in 50–100 mL of 5% glucose IV over 10 minutes, with cardiac monitoring. This can be repeated
until the patient is asymptomatic. It should be followed with a calcium gluconate infusion.
Oral calcium replacement can be given in mild hypocalcaemia.
If there is concurrent hypomagnesaemia, then this should also be corrected with IV magnesium sulphate.
Chronic management
In the long-term, hypoparathyroidism is managed medically. The typical treatment for the majority of patients is active
vitamin D analogue therapy (e.g. calcitriol, alfacalcidol) in varying doses. Doses are titrated to obtain serum calcium levels
in the lower half or slightly below the reference range. 9
The dose of vitamin D analogues is usually within the range of 0.5-2
micrograms daily, but the exact dosing is dependent on clinical response.
Patients should be advised to maintain a calcium-rich diet. Calcium supplements can also be prescribed, but su
dietary calcium intake is adequate for most.
7
PTH replacement therapy can be considered in patients who are not adequately controlled by conventional therapy.
Inadequate control may include any one of\:
1, 9
Symptomatic hypocalcaemia
Hyperphosphatemia
Renal insu
Hypercalciuria
Poor quality of life

Complications

Hypoparathyroidism is associated with complications a
1, 5, 10Cardiovascular complications\: hypocalcaemia can lead to ECG abnormalities, including QTc prolongation, cardiac
arrhythmias and death. Hypoparathyroidism and hypocalcaemia also increase the risk of cardiovascular disease,
ischaemic heart disease and stroke.
Chronic kidney disease
Renal calculi
Cataracts\: seen more commonly in patients with chronic hypoparathyroidism
Neuromuscular complications\: hypocalcaemia can lead to seizures, tetany, and muscle sti
Neuropsychiatric complications\: increased incidence of anxiety, depression and bipolar disorder has been observed in
hypoparathyroidism
Basal ganglia calci
Infections\: some studies have suggested that chronic hypoparathyroidism is associated with an increased risk of
infections, especially urinary tract and respiratory tract infections

References

Khan AA, Bilezikian JP, Brandi ML, et al. E v a l u a t i o n a n d M a n a g e m e n t o f H y p o p a r a t h y r o i d i s m S u m m a r y S t a t e m e n t a n d
G u i d e l i n e s f r o m t h e S e c o n d I n t e r n a t i o n a l W o r k s h o p . J Bone Miner Res. 2022;37(12)\:2568-85.
Bjornsdottir S, Ing S, Mitchell DM, et al. E p i d e m i o l o g y a n d F i n a n c i a l B u r d e n o f A d u l t C h r o n i c H y p o p a r a t h y r o i d i s m . J Bone
Miner Res. 2022;37(12)\:2602-14.
Clarke BL, Brown EM, Collins MT, et al. E p i d e m i o l o g y a n d D i a g n o s i s o f H y p o p a r a t h y r o i d i s m . J Clin Endocrinol Metab.
2016;101(6)\:2284-99.
Bilezikian JP. H y p o p a r a t h y r o i d i s m . J Clin Endocrinol Metab. 2020;105(6)\:1722-36.
Tidy C. H y p o p a r a t h y r o i d i s m . Patient.info. 2021. Available from [LINK].
Abate EG, Clarke BL. R e v i e w o f H y p o p a r a t h y r o i d i s m . Front Endocrinol (Lausanne). 2016;7\:172.
Owen K, Turner H, Wass J. O x f o r d H a n d b o o k o f E n d o c r i n o l o g y a n d D i a b e t e s . Oxford University Press; 2022.
Hendy GN, Cole DE, Bastepe M. Hy p o p a r a t h y r o i d i s m a n d P s e u d o h y p o p a r a t h y r o i d i s m . 2017. Available from [LINK].
Khan AA, Guyatt G, Ali DS, et al. M a n a g e m e n t o f H y p o p a r a t h y r o i d i s m . J Bone Miner Res. 2022;37(12)\:2663-77.
Underbjerg L, Sikjaer T, Mosekilde L, et al. P o s t s u r g i c a l h y p o p a r a t h y r o i d i s m-r i s k o f f r a c t u r e s , p s y c h i a t r i c d i s e a s e s , c a t a r a c t , a n d i n f e c t i o n s . J Bone Miner Res. 2014;29(11)\:2504-10.
c a n c e r ,

Reviewer

Dr Thazin Wynn
Specialist Registrar in Diabetes and Endocrinology

Acromegaly
Addison's Disease (Primary Adrenal Insu
Cushing's Syndrome
Diabetes Insipidus
Growth Hormone De

Test yourselfContents

Introduction
Aetiology
Risk factors
Clinical features
Di
I ti ti
Source\: geekymedics.com