The document provides an extensive overview of parathyroid disorders, including their anatomy, physiology, causes, and management strategies. It details hypercalcemia conditions and differentiates between primary, secondary, and tertiary hyperparathyroidism while discussing associated clinical presentations and treatment options. Additionally, it outlines the pathophysiology, diagnosis, and management approaches for secondary hyperparathyroidism related to chronic kidney disease.

1. PA R AT H Y R O I D D I S O R D E R S
P R E S E N T E D B Y
N U R U L H I D A Y U B I N T I I B R A H I M
N I K N O R L I Y A N A B I N T I S U H A I M I
M A N A G E M E N T O F

2. O U T L I N E
1. Anatomy of parathyroid & physiology of calcium metabolism
2. Causes of hypercalcaemia
3. Features of hypercalcaemia
4. Primary hyperparathyroidism - Parathyroid Adenoma
5. Secondary hyperparathyroidism
6. Tertiary hyperparathyroidism
7. Parathyroid carcinoma

3. WHAT ARE PARATHYROID GLANDS?
ANATOMY
The parathyroid glands are small endocrine glands located in the anterior neck. They are
responsible for the production of parathyroid hormone, which acts to control calcium levels in
the body.
ANATOMICAL LOCATIONS
 Two pairs located on the posterior aspect of the
lateral lobes of the thyroid gland.
 Yellowish-brown, flat ovoid in shape
 4 parathyroid glands ; 2 superior & 2 inferior
Superior parathyroid glands
 Derived embryologically from the fourth pharyngeal pouch
 Located approximately 1cm superior to the entry of the
inferior thyroid arteries into the thyroid gland (at level of
the inferior border of the cricoid cartilage).
Inferior parathyroid glands
 Derived embryologically from the third pharyngeal pouch
 Usually found near the inferior poles of the thyroid gland

4. VASCULAR SUPPLY
ANATOMY
LYMPHATIC DRAINAGE
Every parathyroid gland is supplied by a branch from the inferior thyroid artery
The lymphatic vessels of the parathyroid glands drain (along with those of the thyroid gland)
into the deep cervical lymph nodes and paratracheal lymph nodes.

5. CALCIUM HOMEOSTASIS

6. PARATHYROID GLANDSINTRODUCTIONCALCIUM HOMEOSTASIS
The parathyroid glands produce and secrete PTH, a peptide hormone, in response to
low blood calcium levels
PTH secretion causes the
release of calcium from the
bones by stimulating
osteoclasts, which secrete
enzymes that degrade bone
and release calcium into the
interstitial fluid.
PTH also inhibits osteoblasts,
the cells involved in bone
deposition, thereby sparing
blood calcium.
PTH causes increased
reabsorption of calcium
(and magnesium) in the
kidney tubules from the
urine filtrate.
In addition, PTH initiates the
production of the steroid
hormone calcitriol (also
known as 1,25-
dihydroxyvitamin D), which
is the active form of vitamin
D3, in the kidneys.
Calcitriol then stimulates
increased absorption of
dietary calcium by the
intestines.
1 2 3

7. PARATHYROID GLANDSCALCIUM HOMEOSTASISCALCIUM HOMEOSTASIS

8. HYPERCALCAEMIA
CAUSES OF HYPERCALCAEMIA
ENDOCRINE
MALIGNANCY
 Hyperparathyroidism
 MEN 1
 Familial Hypocalciuric Hypercalcemia
 Metastases
 PTHrP
 Breast cancer, Lung cancer,
Bone cancer
GRANULOMATOUS DISEASE
 Sarcoidosis
 Tuberculosis
MISCELLANEOUS
 Acute Kidney Failure
 Milk-Alkali Syndrome
 Lithium therapy
 Thiazides
Increase sodium and water reabsorption
and increase calcium concentration
 Vitamin D
MEN 1
Multiple Endocrine Neoplasia Type 1
 Parathyroid Adenoma
 Pituitary Adenoma
 Pancreatic Islet Cell Tumor
HYPERCALCAEMIA
DRUGS

9. PARATHYROID GLANDSCLINICAL PRESENTATIONS
"Stones, Bones, Abdominal Moans, And Psychic Groans"
OF HYPERCALCAEMIA
The presentation in a patient with hypercalcaemia varies with how fast and how far the calcium
level rises, as well as the sensitivity of the individual to elevated calcium levels.
C N S
 Lethargy
 Weakness
 Confusion
 Coma
R E N A L
 Polyuria
 Nocturia
 Dehydration
 Renal stones
 Renal failure
G I T
 Constipation
 Nausea
 Anorexia
 Pancreatitis
 Gastric Ulcer
CLINICAL PRESENTATION

10. HYPERPARATHYROIDISM
P r i m a r y S e c o n d a r y
Primary hyperparathyroidism is
the unregulated overproduction
of parathyroid hormone (PTH)
resulting in abnormal calcium
homeostasis.
Secondary hyperparathyroidism is
the overproduction of parathyroid
hormone secondary to
hypocalcaemia.
Te r t i a r y

11. HYPERPARATHYR OI DI SM
P R I M A RY

12. PARATHYROID GLANDSINTRODUCTION
Primary hyperparathyroidism is defined as hypercalcemia in the presence of
an unsuppressed or elevated level of PTH.
CAUSES OF PRIMARY HYPERPARATHYROIDISM?
More commonly sporadic than familial
 Single parathyroid adenoma (~85%) (most common)
 Double or triple adenoma
 Parathyroid hyperplasia (~13%)
 Parathyroid carcinoma (less than 1%)
 MEN-1
 MEN-2A
 Familial hyperparathyroidism
 Patients usually present in the 5th or 6th decades
 Female predominance with a ratio of 3:1.
 Typically identified incidentally
(elevated total calcium or following routine assessment of bone densitometry (DEXA scan)
 Symptomatic – kidney stones remain the most common clinical manifestation
The histological differentiation between adenoma and hyperplasia can be difficult and the macroscopic findings are an important
determinant in making the diagnosis.
 A single enlarged gland with three small normal glands is characteristic of a single adenoma (multiple adenomas occur more
frequently in older patients)
 Parathyroid hyperplasia by definition affects all four glands.
REFERENCES:
BAILEY & LOVE 27TH EDITION
HTTP://ENDOCRINEDISEASES.ORG/PARATHYROID/PARATHYROID_PHP.SHTML

13. PARATHYROID GLANDS
Multiple Endocrine Neoplasia
(MEN 1)
1. Parathyroid adenoma
2. Pituitary adenoma
3. Pancreatic islet cell tumor
MULTIPLE ENDOCRINE
Multiple Endocrine Neoplasia
(MEN 2)
1. Parathyroid adenoma
2. Thyroid medullary carcinoma
3. Pheochromocytoma
NEOPLASIA

14. PARATHYROID GLANDS
RISK FACTORS (things to rule out in history taking)
1. Age
2. Gender (female > male)
3. Radiation therapy to head, neck or chest
4. Use of lithium
5. Family history
REFERENCES:
BAILEY & LOVE 27TH EDITION
HTTP://ENDOCRINEDISEASES.ORG/PARATHYROID/PARATHYROID_PHP.SHTML
PRIMARY HYPERPARATHYROIDISM
PHYSICAL EXAMINATION
 Physical examination findings are usually
noncontributory.
 Examination may reveal muscle weakness and
depression.
 A palpable neck mass is not usually expected with
hyperparathyroidism, although in rare cases, it may
indicate parathyroid cancer.
HYPERCALCEMIC CRISIS
Patient with PHPT may present acutely
with nausea, vomiting, fatigue, muscle
weakness, confusion and a decreased
level of consciousness – a complex
referred to as hypercalcaemia crisis
Serum calcium > 4.5mmol/L
Cardiac arrest and coma can occur
1. Increasing renal excretion of calcium
2. Reducing skeletal release of calcium
3. Treatment of underlying cause
TREATMENT

15. PARATHYROID GLANDS
BLOOD TESTS
REFERENCE:
BAILEY & LOVE 27TH EDITION
DIAGNOSIS
1. Serum calcium
2. Parathyroid hormone
3. Serum phosphate
4. Liver function test – alkaline phosphatase
SKELETAL ASSESSMENT
Bone density testing is usually recommended
 Bone densitometry or x-ray
 This test can help determine if the bones have
become weakened as a result of abnormal blood
calcium levels.
Primary hyperparathyroidism is a biochemical diagnosis

16. PARATHYROID GLANDS
KIDNEY ASSESSMENT
REFERENCE:
BAILEY & LOVE 27TH EDITION
DIAGNOSIS
LOCALIZATION STUDIES
Primary hyperparathyroidism is a biochemical diagnosis
Hypercalcaemia may adversely affect kidney function
 24-hour urinary excretion – assess hypercalciuria / risk of stones
 Serum creatinine – assess renal function
Pre-operative identification to guide the type of surgery
1. Nuclear medicine based studies – accumulates in mitochondria and washes out
depending on the number of mitochondria in individual tissues.
2. Ultrasound – parathyroid adenomas are typically oval or elongated, bi or
multilobed hyperechoic structures.
3. 4D CT scanning – gives both anatomical as well as functional information about
the parathyroid glands.

17. PARATHYROID GLANDS
NON-SURGICAL MANAGEMENT
REFERENCE:
BAILEY & LOVE 27TH EDITION
MANAGEMENT
Non-surgical treatment may be recommended for people who have no symptoms and
whose blood calcium is only mildly elevated, provided they do not have;
 Low bone density
 Asymptomatic vertebral fractures
 Impaired renal function
 Silent kidney stones
GENERAL MEASURES
 Avoid lithium
 Avoid excessive loss of body fluids
 Minimize bone loss by remaining active.
 Drink an adequate amount of fluid throughout
the day.
 Maintain a moderate calcium intake
(approximately 1000 mg of elemental
calcium/day)
 Consume a moderate amount of vitamin D (400
to 600 international units, or 10 to 15 mg daily)
SURGICAL TREATMENT
Surgery is recommended for people with
symptoms.

18. PARATHYROID GLANDS
REFERENCE:
BAILEY & LOVE 27TH EDITION
MANAGEMENT
Bilateral neck exploration – required where imaging is negative or discordant, MEN, lithium
induced PHPT.
• Transverse collar (kocher’s) incision is made
• All four gland are identified.
• 31/2 are removed with remaining ½ of vascularized parathyroid left insitu
• Alternatively all four glands can be removed and a forearm autotransplant can be created
where small pieces of parathyroid are sutured into pockets created in the brachioradialis
muscle
Minimally invasive parathyroidectomy – commonly refers to the removal of a localized abnormal
parathyroid gland through an
• Incision less than 3cm in length.
• Includes open approach (central and lateral incisions), video assisted and radio-guided
parathyroidectomy.
• Once the abnormal gland is removed, intra-operative PTH should be measured. If it does not
fall then cervical exploration might be required.

19. HYPERPARATHYR OI DI SM
S E C O N D A RY

20. INTRODUCTION
 Secondary hyperparathyroidism is defined as a
derangement in calcium homeostasis, which leads to
a compensatory increase in PTH secretion. It occurs
primarily as a result of chronic kidney disease and is
therefore sometimes referred to as renal
hyperparathyroidism.
 A disease outside of the parathyroid causes all of
the parathyroid glands to become enlarged and
hyperactive.
Bailey & Love 27th Edition

21. ETIOLOGY
 Chronic kidney disease
 GI Malabsorption – Celiac disease, short bowel syndrome
 Crohn’s disease
 Severe vitamin D deficiency – Inadequate sunlight
exposure and diet
 Liver disease
 Chronic lithium usage

22. ETIOLOGY
 It is seen in patients with chronic kidney disease where the failing
kidneys do not convert vitamin D to its active form and they do not
excrete phosphate.
 The pathological characteristics associated with secondary
hyperparathyroidism include hyperplasia, asymmetrical glandular
enlargement or nodularity  when the parathyroid gland becomes
nodular it loses expression of the vitamin D and Ca receptors.
 It has been proposed that nodular parathyroid glands may be
resistant to calcimimetics and therefore be refractory to medical
management.
Bailey & Love 27th Edition

23. CALCIUM & PHOSPHORUS
IN RENAL FAILURE

24. PATHOPHYSIOLOGY

25. HOW TO DIAGNOSE?
 Hypercalcemia
 Pruritus
 Extra-skeletal calcification
 Painful, broken, fractured bones
 Chvostek sign / trousseau sign
 Features of chronic renal failure
 Features of underlying
malabsorption syndrome
CLINICAL MANIFESTATION

26. HOW TO DIAGNOSE?
 The diagnosis of secondary
hyperparathyroidism is a biochemical.
 The diagnosis of secondary
hyperparathyroidism is characterized by
hypocalcaemia or normocalcaemia with
an elevated PTH.
 Patients have a high serum phosphate
and a low vitamin D.
 A neck ultrasound can be performed to
identify patients with nodular hyperplasia
who may be refractory to medical
management.
INVESTIGATIONS
 Blood test (renal function test)
 High phosphate
 High creatinine, urea, nitrogen
 Low magnesium
 Serum calcium
 Serum PTH
 Alkaline phosphatase
 Serum 25-hydroxyvitamin D
 Ultrasound neck
 X-ray bone

27. HOW TO DIAGNOSE?
Traditional plain x-rays now rarely demonstrate the
pathognomonic osteitis fibrosa cystica. However, bone
densitometry (DEXA scan) typically demonstrates osteopenia or
osteoporosis.
-4
+1 DEXA SCAN RESULT

28. MANAGEMENT
Treatment of secondary hyperparathyroidism in CKD should
start at the beginning of stage 3 of CKD.
It can be divided into 3 steps:
1. Optimize the levels of serum calcium and phosphate
2. Control PTH and vitamin D level
3. Surgical - Parathyroidectomy

29. MANAGEMENT
 Through dietary restriction of phosphorous and
using phosphate binders.
 Patients with CKD stage 3 and 4 has serum
phosphorous > 4.6 mg/dl while patient with CKD
stage 5 has serum phosphorus > 5.5 mg/dl
 Dietary restriction of phosphorous should be 800 –
1000 mg/day
Normal level of
serum phosphorous
2.5 to 4.5 mg/dL
1st STEP : To optimize the levels of serum phosphate and calcium

30. MANAGEMENT

31. PHOSPHATE BINDERS
 Phosphate binders is the main stay of therapy in secondary
hyperparathyroidism in CKD patient.
 These agents work by binding to phosphate in the GI tract, thereby
making it unavailable to the body for absorption. Hence, these drugs are
usually taken with meals to bind any phosphate that may be present in
the ingested food.
Calcium-Based Binders Metal-Based Binders Calcium-Free and Metal-
Free Binders
 Calcium Carbonate
 Calcium Acetate (Royen)
 Calcium
acetate/magnesium
carbonate (Osvaren)
 Aluminium
 Lanthanum (Fosrenol)
 Sevelamer : Chlorhydrate
(Renagel)
 Carbonate (Renvela)

32. PHOSPHATE BINDERS
 Lanthanum carbonate is indicated for the reduction of high phosphorus levels
in patients with end-stage renal disease. It directly binds dietary phosphorus
in the upper gastrointestinal tract, thereby inhibiting phosphorus absorption.
 Aluminium toxicity (Serum aluminum >50-60 µg/L) leads to severe refractory
microcytic anemia, osteomalacia and dementia  start chelation therapy
(deferoxamine).
 Deferoxamine can be used in iron and aluminium toxicity and it has a high
affinity for ferric iron and does not affect iron in hemoglobin or cytochromes.

33. MANAGEMENT
 However, treatment of secondary hyperparathyroidism with
calcitriol and calcium-based phosphate binders can produce
hypercalcemia and over suppression of PTH, which results in
adynamic bone that cannot buffer calcium and phosphate levels,
and increased risk of vascular calcification.
 PTH levels must, therefore, be reduced to within a range that
supports normal bone turnover and minimizes ectopic
calcification.
 Vitamin D analogs that inhibit PTH gene transcription and
parathyroid hyperplasia (and have reduced calcemic activity) are a
safer treatment for secondary hyperparathyroidism.
US National Library of Medicine National Institutes of Health

34. MANAGEMENT
2ND STEP : Control PTH and Vitamin D level
 Vitamin D analogues + calcimimetic agents
 Calcitriol deficiency and resistance are the major contributors to the
pathophysiology of the disease.
 Calcitriol is the natural form of vitamin D produced by the human body.
IV administration is more effective than oral calcitriol
 Ergocalciferol is vitamin D2 or nutritional/supplemental vitamin D and
only indicated if calcitriol levels <30 ng/ml
NKF KDOQI GUIDELINES

35. VITAMIN D ANALOGUES

36. VITAMIN D ANALOGUES
Selective agents have more affinity towards kidney rather
than intestinal receptors.

37. CALCIMIMETICS
Calcimimetics are the newer agents that
allosterically increase the sensitivity to
calcium and calcium sensing receptors in
the parathyroid gland thus supressing
PTH.
Mimics the calcium in the blood
It alter the set point of the CaR 
reducing the constant stimulation of the
parathyroid glands  lowering the PTH
level.
Most common side effects:
 Bone & muscle aches
 Diarrhea
 Respiratory tract infection

38. PARATHYROIDECTOMY
Indications:
ESSENTIAL COMPONENTS CLINICAL FINDINGS
1. Persistently high serum level of
intact PTH >500 pg/mL
2. Hyperphosphataemia (serum P
>6 mg/dL) or hypercalcaemia
(serum Ca >2.5 mmol/L or 10
mg/dL) which is refractory to
medical management
3. Estimated volume of the largest
gland >300–500 or long axis >1
cm
If patients have one of these symptoms,
parathyroidectomy should be
recommended:
 Severe osteitis fibrosa with associated
high bone turnover
 Subjective symptoms (bone and joint
pain, arthralgia, muscle
 weakness, irritability, purititis,
depression)
 Progressive ectopic calcification
 Calciphylaxis
 Progressive reduction in bone mineral
content
 Anaemia resistant to erythropoietin
stimulating agent (ESA)
 Dilated cardiomyopathy/cardiac failure

39. PARATHYROIDECTOMY
Subtotal
parathyroidectomy
Total
parathyroidectomy
+
Autotransplantation
Remain surgical intervention of
choice when indicated
The preferred reimplantation site
is still the sternocleidomastoid or
from the brachioradialis muscle

40. A subtotal parathyroidectomy is where three and a half
parathyroid glands are excised, with the remnant being marked
with a non-absorbable stitch to facilitate identification in the event
of recurrent disease.
A biopsy of the final gland that is to
be left in situ is mandatory to confirm
the presence of residual parathyroid
tissue. Ideally an inferior gland is left
in situ to facilitate reoperative surgery
and minimize potential damage to the
recurrent laryngeal nerve in that
setting.
PARATHYROIDECTOMY
SUBTOTAL

41. PARATHYROIDECTOMY
 Overall, regardless of the operative approach utilized the cure
rate ranges between 90% and 96%, with similar complication
rates.
 A randomized study looking at 40 patients who either
underwent a subtotal or total parathyroidectomy with auto-
transplant demonstrated no significant difference between the
two operations in terms of efficacy and recurrence rate
(Rothmund et al., 1991).
 Monitoring of calcium levels is important in follow up after
surgery.

42. MANAGEMENT SUMMARY
 Mainstay of treatment for ESRD is renal transplantation.
Medical management with calcium and vitamin D
replacements and phosphate binders is a bridge to
transplantation.
 Use of calcimimetics has reduced the requirement for
surgical intervention.
 Subtotal paratyroidectomy is the surgical intervention of
choice.

43. P R E S E N T E D B Y
N U R U L H I D A Y U
T E R T I A R Y
H Y P E R P A R AT H Y R O I D I S M

44. PARATHYROID GLANDSTERTIARY
HYPERPARATHYROIDISM
AETIOLOGY
The etiology is unknown but may be due to monoclonal expansion of parathyroid cells (nodule
formation within hyperplastic glands). A change may occur in the set point of the calcium-
sensing mechanism to hypercalcemic levels. Four-gland involvement occurs in most patients.
Tertiary hyperparathyroidism is a state of excessive secretion of parathyroid hormone (PTH)
after a long period of secondary hyperparathyroidism and resulting in a high blood calcium
level. It reflects development of autonomous (unregulated) parathyroid function following a
period of persistent parathyroid stimulation. No longer response to medical therapy.
Tertiary hyperparathyroidism is observed most
commonly in patients with chronic secondary
hyperparathyroidism who have been on dialysis therapy
for years. The hypertrophied parathyroid glands enlarge
over time and continue to over secrete parathyroid
hormone, despite serum calcium levels that are within
the reference range or even elevated.
PATHOPHYSIOLOGY MANAGEMENT
Total parathyroidectomy with
autotransplantation or
subtotal parathyroidectomy if
indicated.

45. P R E S E N T E D B Y
N U R U L H I D A Y U
P A R AT H Y R O I D C A R C I N O M A

46. PARATHYROID GLANDSPARATHYROID
 Cancer of parathyroid accounts for 1% of cases of hyperparathyroidism
 A rare cause of primary hyperparathyroidism, which is usually caused by
a parathyroid adenoma and occasionally by primary parathyroid
hyperplasia. Other causes are parathyroid cyst and ectopic secretion of
parathyroid hormone (PTH) from a non-parathyroid tumor.
 A history of previous neck irradiation remains the only known
environmental risk factor.
 Features: High calcium & PTH, palpable neck swelling (36-52%), and
occasionally lymphadenopathy
CARCINOMA

47. PARATHYROID GLANDSPARATHYROID
CARCINOMA
 The tumours remain difficult to diagnose preoperatively
(histologically) as they biochemically resemble primary
hyperparathyroidism
 The leading cause of morbidity and mortality from parathyroid
carcinoma is hypercalcaemia, due to inappropriate PTH secretion.
 Treatment is focused on controlling hypercalcaemia and removal
of the carcinoma where possible.
 Surgery remains the mainstay of treatment for primary
presentations and locally recurrent disease.

48. PARATHYROID GLANDSPARATHYROID
CARCINOMA
 Complete resection of the tumour avoiding spillage is vital in
preventing seeding and thus recurrent disease. En bloc resection
of the tumour, associated thyroid lobectomy and central neck
dissection remains controversial.
 Adjuvant chemotherapy has not been shown to confer a disease-
free or overall survival benefit.

49. PARATHYROID GLANDSPARATHYROID
CARCINOMA
 Untreated, parathyroid carcinoma  severe hyperparathyroidism,
with signs and symptoms including hypercalcemia, bone pain,
osteoporosis, fractures, and kidney stones or other renal damage.
The diagnosis is often not made prior to parathyroidectomy.
 Recurrences may be treated by local excision or ablative (eg,
radiofrequency) treatments. Death is usually caused by medically
refractory hypercalcemia and seldom tumor burden alone.

50. SUMMARY

51. PARATHYROID GLANDSREFERENCE
 BAILEY & LOVE’S 27th EDITION
 EMEDICINE
 UPTODATE
 MAYOCLINIC
 AMERICAN ENDOCRINE ASSOCIATION
 MIMS MALAYSIA

52. T H A N K Y O U