simplified

1. Disorders of Parathyroid Gland
by Dr Irum siddiquie
PGR Pediatrics

2. Objectives
• To familiarize with physiology of gland
• Describe the differential diagnosis of
parathyroid diseases that result in hyper- and
hypocalcemia
• Delineate the approach to making the
diagnosis of parathyroid diseases and
necessary therapies

3. Main regulators of calcium and phosphate
homeostasis in body
– PTH
– Vitamin D
– Calcitonin

4. Vitamin D- Actions---Calcitriol
Increases intestinal
absorption of calcium
and phosphate by
increasing synthesis
of calcium binding
proteins
Mineralization of
bone at low doses
Mobilization of
calcium from bone
at high doses
Increases re-
absorption of
calcium and
phosphorous
Decrease excretion
of calcium and
phosphorous

5. Parathyroid hormone
Kidneys
• Increases calcium Re-absorption
• Inhibits phosphate Re-absorption
• Increases activity of 1 alpha-hydroxalase
Bone
• Stimulates bone Resorption
• Increases serum calcium levels
Intestine
• INDIRECT Effect through calcitriol

6. Hypoparathyroidism

7. Decrease in extracellular
calcium concentration
Detected by the membrane
bound CaSR
Releasing preformed PTH
into blood
Failure of the glands to
respond
HYPOPARATHYROIDISM

8. Clinical Presentation
• Tetany---classic neuromuscular findings---sustained or
intermittent involuntary contractions
• Seizures
– short, lasting 1 minute or less, but repetitive initial
lack of a postictal phase
• Fatigue ,lethargic
• Signs of Rickets
• Stridor with partial occlusion
• Cyanosis with complete occlusion
• Bronchospasm can present as Wheezing

9. Clinical signs
– Chvostek sign
– Trousseau sign

10. Laboratory findings
• Shortened fourth and fifth metacarpals and
metatarsal (Pseudohypoparathyroidism)
• Prolongation of QT interval on electrocardiography
• Hypocalcemia, Hyperphosphatemia with Alkaline
phosphatase in the normal range
• Calcifications of the basal ganglia in longstanding
cases (generally >8 years) contribute to (cognitive)
dysfunction

11. Differential diagnosis

12. AHO:Albright hereditary osteodystrophy PHP :pseudohypoparathyroidis

13. Chromosomal Microdeletions
(22q11.2,10p15.3p14)
Hypoplastic or Absent parathyroid glands
DiGeorge syndrome
• Cardiac abnormality (commonly interrupted aortic arch,
truncus arteriosus and tetralogy of Fallot)
• Abnormal facies
• Thymic aplasia
• Cleft palate
• Hypocalcemia/Hypoparathyroidism

14. • Barakat syndrome
– Deletion of the gene coding for GATA3
– the Triad of Hypoparathyroidism, Deafness, and Renal
dysplasia
• Sanjad-Sakati syndrome
– Mutations in the gene encoding TBCE
– Hypoparathyroidism ,Failure to thrive, Microcephaly,
and Marked intellectual disability
• Kenny-Caffey syndrome
– Normal intelligence
– Marked by thickened long bones at birth
Congenital causes

15. Mitochondrial Cytopathies
• Kearns-sayre syndrome
• MELAS
• Should be considered in patients with unexplained symptoms
– Ophtalmoplegia
– Sensrineural hearing loss
– Cardiac function disturbances
– Tetany

16. – Gain-offunction mutations in the CaSR gene result
in Diminished parathyroid responsiveness to low
calcium concentrations
– Gene coding for PTH is mutated, resulting in a non-
functional or absent circulating product

17. Acquired causes
• Iatrogenic
• Non Iatrogenic
– Transient
– Infiltrative
– Destructive

18. Iatrogenic causes
• Intentional surgical removal-----for the
treatment of parathyroid hyperplasia
• Accidental destruction---during
Thyroidectomy or tumor resection
• Treatment of chronic anemia such as
Thalassemia with repeated blood transfusions -
---Iron overload---if concomitant iron
chelation therapy is not provided

19. Non-iatrogenic
Transient
• Maternal Hypercalcemia during pregnancy
• Abnormal concentrations of magnesium (both hypo-
and hypermagnesemia)
• Metals such as copper in patients with poorly
treated Wilson disease accumulate in the
parathyroid glands, causing loss of function
(reversible with treatment)

20. Infiltrative
– Neck tumors and granulomatous diseases may invade
the parathyroids

21. Destructive
Polyglandular autoimmune syndrome type I
• Dysfunctional product ofthe AIRE (autoimmune regulator)
gene
• Chronic mucocutaneous candidiasis (nails,mouth,intestine,
vagina)
• Adrenal failure

22. Treatment
• Calcium supplementation for documented
hypocalcemia
• Vitamin D supplementation with calcitriol
• Careful monitoring of serum calcium and
phosphorous during therapy
• Monitor urine calcium levels to avoid
hypercalciuria

23. Pseudo-Hypoparathyroidism (PHP)

24. Pseudo-Hypoparathyroidism (PHP)
PTH is produced and released into the
circulation appropriately
fails to have calcemic effects
Genetic defect in hormone receptor
adenylate cyclase system

25. • Autosomal dominant
• The disorders can be categorized by their
(lack of) renal responsiveness to exogenously
administered PTH

26. Type IA
– Albright hereditary osteodystrophy.
– Lack of adequate expression of the a subunit of
the G-protein that is responsible for PTH signal
transduction
Type IB
– The Biochemical profile is the same
– No phenotype correlation.

27. Clinical Presentation
• Attributable to
Hypocalcemia
• Short, stocky build
• Round face

28. •Brachydactyly with
dimpling of dorsum of
hand
•Short wide
phalanges
•Short 2nd
metacarpal and
metatarsal

29. • Thickening of calvaria
• Subcutaneous calcium deposits and
metaplastic bone formation
• Calcification of basal ganglia and lenticular
catarcts

30. Diagnosis
– Hypocalcemia
– Phosphorous and Alkaline phosphatase
elevated
– Confirmation: lack of response to
exogenously admnistered PTH
– Definitive diagnosis: Demonstaration of
mutated G protein

31. Treatment
• Calcitriol together with an oral source of
• Calcium
Careful follow-up assessment
• Blood and Urine calcium concentrations to
monitor for hypercalcemia/hypercalciuria
complications

32. Pseudo-pseudo
Hypoparathyroidism

33. Pseudo-pseudo hypoparathyroidism
– Phenotypically similar but metabolically dissimilar
– Usual anatomic stigmata of PHP
– Members of same family
– But serum calcium and phosphorous are normal
– PTH slightly elevated
– Transition from normocalcemia to hypercalcemia
may occur with age

34. Hyper-Parathyroidism

35. TYPE OF
HYPERPARATHYROIDISM DIFFERENTIAL DIAGNOSIS
Primary Parathyroid adenoma
Parathyroid hyperplasia
Secondary Vitamin D deficiency
1-a-hydroxylase deficiency
Chronic kidney disease
Malabsorption
Hereditary vitamin D-resistant rickets
Malnutrition
Medications affecting vitamin-D
metabolism
Tertiary Renal failure

36. Primary hyperparathyroidism
• Serum calcium and PTH concentrations are
concomitantly high
• Causes
• Parathyroid hyperplasia/adenoma
• Parathyroid carcinoma

37. Primary Hyperparathyroidism
Symptoms
• Abdominal pain, Constipation
• Nausea and Vomiting
• Flank pain, Hematuria , Polyuria
• Fatigue, Depression, and Hypertension-related headache
• Changes in mentation progressing to stupor and coma

38. Clinical Signs
• Weakness, Loss of reflexes
• Bradycardia
• Band keratopathy
• Bone disease
– generalized demineralization and subperiosteal resorption
– With prolonged disease, cysts with a hemorrhagic
component, known as brown tumors, on radiography

39. Genetic syndromes associated with primary
hyperparathyroidism
• Multiple endocrine neoplasia (MEN-1)
• MEN 2-A
• Hyperparathyroidism Jaw-Tumor syndrome

40. MEN-1
• Pituitary tumors, Insulinomas, Gastrinomas
• mutations in the MENIN gene (tumor suppressor
gene)
• presents in the second to third decade, although it
has been described in the first decade
• Treatment is Surgical removal

41. MEN-2A
– Medullary thyroid carcinoma
– Pheochromocytoma
– Parathyroid adenoma

42. Jaw-tumor syndrome
– Autosomal dominant
– has a higher risk for both parathyroid carcinoma and
adenoma
– Fibro-osseous jaw tumors
– May also have Polycystic kidney disease ,Renal
hemartomas, Wilms tumor
– Treatment : Surgical removal

43. Secondary hyperparathyroidism
• Appropriately elevated PTH values in response to
low calcium concentrations
• Causes:
– Vitamin D deficiency
– 1-a-hydroxylase deficiency
– Chronic kidney disease
– Malabsorption
– Hereditary vitamin D-resistant rickets
– Malnutrition
– Medications affecting vitamin-D metabolism

44. Biochemical evaluation
– Total and ionized calcium, electrolytes
– Renal and liver function tests
– Serum phosphate, 25-hydroxyvitamin D,
1,25Di-hydroxyvitamin D
– Magnesium
– Urine calcium and creatinine

45. Treatment
• Calcium-vitamin D supplementation
• Administration of calcitriol---depending on
the cause

46. Tertiary hyperparathyroidism
• Occurs in the setting of persistent secondary
hyperparathyroidism leading to parathyroid hyperplasia and
subsequent autonomous PTH secretion
• Incidence: 0.5% to 5.6% of patients after renal transplant
• Elevated serum calcium and elevated to inappropriately
normal PTH (the history in this case is what differentiates
the two entities)
• Causes: Chronic kidney disease
• Treatment may involve parathyroidectomy or, in some cases,
calcimimetics

48. TYPE OF
HYPERPARAT
HYROIDISM
CALCIUM PHOSPHORU
S
CALCITRIOL ALKALINE
PHOSPHATA
SE
URINE
CALCIUM/CR
EATININE
RATIO
Primary High Low High/Normal High High
Secondary Normal/Low Low High/Normal High Low
Tertiary High Low High/Normal High High

49. Questions

50. A 9-year-old boy presents to the emergency
department with diffuse abdominal pain, nausea, and
vomiting 2 hours after sustaining blunt trauma to the
abdomen when he fell off his bike and hit the
handlebars. Laboratory studies show elevated
amylase, lipase, and hypocalcemia. He is diagnosed
with acute pancreatitis and admitted for intravenous
fluid hydration and management. Which of the
following findings is expected to be seen as a result
of the hypocalcemia?
A. Decreased QTc interval on electrocardiography
B. Normal or slightly decreased phosphorus
C. Positive Trousseau sign
D. Rigidity of fingers (cannot be bent)
E. Hypophosphatemia

51. You are called to the newborn nursery to evaluate a 3-day-old
newborn who was noted by the nursing staff to have twitching of both
hands. She was born at term via repeat cesarean delivery. On physical
examination, she is mildly cyanotic and has a mild cleft palate. Heart
examination documents a grade III/VI murmur. Laboratory studies
reveal calcium of 6.9mg/dL (1.73 mmol/L) and phosphorus of 9 mg/dL
(2.91 mmol/L). The remainder of her electrolyte measurements are
within normal limits, including normal serum glucose and sodium. Which
of the following is the most likely cause of the clinical findings
described in this patient?
A. Maternal hypocalcemia during pregnancy
B. Kenney-Caffey syndrome
C. DiGeorge syndrome
D. Loss-of-function mutations in the parathyroid hormone (PTH)
receptor
E. Sanjad-Sakati syndrome.

52. A 9-month-old boy is brought to the clinic by his consanguineous
parents for the evaluation of multiple subcutaneous nodules that have
been present since birth but are increasing in size. Physical
examination reveals multiple 5- to 7-mm hard subcutaneous nodules
over the extremities. In addition, the patient is at greater than the
95th percentile for weight and less than the 25th percentile for
height. He has a round face with short metacarpals and metatarsals.
He is diagnosed with Albright hereditary osteodystrophy.
Which of the following best describes the pathophysiology of the
pseudohypoparathyroidism seen in patients who carry this diagnosis?
A. Absence of the parathyroid glands
B. Decreased synthesis of PTH
C. Normal PTH release but failure of tissues to respond
D. Normal PTH synthesis but failure to release it
E. Synthesis of defective PTH

53. A 11-year-old girl presents with polyuria, nausea,
vomiting, abdominal pain, and fatigue.Laboratory
studies reveal calcium of 12 mg/dL (3 mmol/L),
phosphorus of 2.1 mg/dL (0.68mmol/L), and urine
calcium/creatinine ratio of 2.2. Which of the
following is the most appropriate next serum
study to order in this patient?
A. Calcium/creatinine ratio
B. Cortisol
C. Insulinlike growth factor 1
D. PTH
E. Thyrotropin

54. Thank you