This document discusses disorders of the parathyroid gland including hypoparathyroidism and hyperparathyroidism. It describes various causes of hypoparathyroidism including genetic disorders, autoimmune disorders, surgical complications, and functional immaturity in infants. Symptoms include low calcium levels, muscle cramps, and seizures. Treatment involves calcium and vitamin D supplementation. Causes of hyperparathyroidism are also outlined such as tumors and genetic disorders. Symptoms include high calcium levels and bone abnormalities. Treatment is surgical removal of the overactive parathyroid gland.

1. .
Disorders of Parathyroid Gland
Dr. Jeetendra K Singh

2. Hypoparathyroidism

3. • The role played by the parathyroid glands in
hypocalcemic infants remains to be clarified,
although functional immaturity of the parathyroid
glands is invoked as one pathogenetic factor.
• Transient idiopathic hypocalcemia (1-8 wk of
age), serum levels of parathyroid hormone
(PTH) are significantly lower than those in
normal infants.

4. • It is possible that the functional immaturity is a
manifestation of a delay in development of the
enzymes that convert glandular PTH to secreted
PTH; other mechanisms are possible.

5. Aplasia/Hypoplasia of Parathyroid Glands
• DiGeorge/velocardiofacial syndrome (1/4000)
• In 90% of patients, the condition is caused by a
deletion of chromosome 22q11.2.
– Approximately 25% of these patients inherit the
chromosomal abnormality from a parent.
• Neonatal hypocalcemia occurs in 60% of
affected patients, but it is transitory in the
majority; hypocalcemia can recur or can have its
onset later in life.

6. • Associated abnormalities of the 3rd and 4th
pharyngeal pouches are common;
Conotruncal defects of the heart in 25%,
Velopharyngeal insufficiency in 32%,
Cleft palate in 9%,
Renal anomalies in 35%, and
Aplasia of the thymus with severe immunodeficiency
in 1%.

7. X-linked Recessive Hypoparathyroidism
• Two large North American pedigrees
• The onset of afebrile seizures characteristically
occurs in infants from 2 wk to 6 mo of age.

8. Autosomal Recessive Hypoparathyroidism
With Dysmorphic Features
• Middle Eastern children
• Profound hypocalcemia occurs early in life
• Dysmorphic features include microcephaly,
deep-set eyes, beaked nose, micrognathia, and
large floppy ears.
• Intrauterine and postnatal growth retardation are
severe, and mental retardation is common.
• Chromosome 1q42-43

9. HDR Syndrome
• Hypoparathyroidism,
• sensorineural Deafness, and
• Renal anomaly
• The GATA3 gene is located at chromosome
10p14.

10. Suppression of neonatal parathyroid hormone
secretion due to maternal hyperparathyroidism
• Transient neonatal hypocalcemia results from
suppression of the fetal parathyroid glands by
exposure to elevated levels of calcium in
maternal and hence fetal serum.
• Tetany usually develops within 3 wk but may be
delayed by 1 mo or more if the infant is breast-
fed.
• Hypocalcemia can persist for weeks or months.

11. Autosomal Dominant Hypoparathyroidism
• Activating (gain-of-function) mutation of the
Ca2+ sensing receptor,
• forcing the receptor to an “on” state with
subsequent depression of PTH secretion even
during hypocalcemia.
• The patients have hypercalciuria.
• The hypocalcemia is usually mild and might not
require treatment beyond childhood.

12. Hypoparathyroidism associated
with Mitochondrial Disorders
• Should be considered in patients with
unexplained symptoms such as
ophthalmoplegia, sensorineural hearing loss,
cardiac conduction disturbances, and tetany

13. Surgical Hypoparathyroidism
• Removal or damage of the parathyroid glands
can complicate thyroidectomy.
• Symptoms of tetany can occur abruptly
postoperatively and may be temporary or
permanent.
• In some instances, symptoms develop
insidiously and go undetected until months after
thyroidectomy.

14. • Deposition of iron pigment or of copper in the
parathyroid glands (thalassemia, Wilson
disease) can produce hypoparathyroidism.

15. Autoimmune Hypoparathyroidism
• Parathyroid antibodies
• Autoimmune polyglandular disease type I
autoimmune polyendocrinopathy, candidiasis,
and ectodermal dystrophy (APCED).
• Autosomal recessive
• AIRE gene (autoimmune regulator);
chromosome 21q22
• One third of patients with this syndrome have all
3 components; 66% have only 2 of 3 conditions.

16. • The candidiasis almost always precedes the
other disorders (70% of cases occur in children
<5 yr of age);
• The hypoparathyroidism (90% after 3 yr of age)
usually occurs before Addison disease (90%
after 6 yr of age).
• Alopecia areata or totalis, malabsorption
disorder, pernicious anemia, gonadal failure,
chronic active hepatitis, vitiligo, and insulin
dependent diabetes

17. Idiopathic Hypoparathyroidism
• No causative mechanism can be defined.
• Autoimmune condition- after few years of life.

18. Clinical Manifestations
• No symptoms to those of complete and long-
standing deficiency.
• Muscular pain and cramps are early
manifestations;
• They progress to numbness, stiffness, and
tingling of the hands and feet.
• Convulsions with or without loss of
consciousness can occur at intervals of days,
weeks, or months.

19. • With long-standing hypocalcemia, the teeth
erupt late and irregularly. Enamel formation is
irregular, and the teeth may be unusually soft.
• The skin may be dry and scaly.
• The candidal infection- nails, oral mucosa,
angles of the mouth, and less often, the skin; it
is difficult to treat.
• Cataracts
• Permanent physical and mental deterioration
occur if initiation of treatment is long delayed.

20. Laboratory Findings
• S. Ca2+ low (5-7 mg/dL)
• Phosphorus level is elevated (7-12 mg/dL).
• S. ALP is normal or low, and
• 1,25(OH)2D3 is usually low.
• Mg
• PTH is low
• Radiographs or CT scans of the skull can reveal
calcifications in the basal ganglia.
• Prolongation of the QT interval on ECG.

21. • EEG- widespread slow activity
• When hypoparathyroidism occurs concurrently
with Addison disease, the serum level of calcium
may be normal, but hypocalcemia appears after
effective treatment of the adrenal insufficiency.

22. Treatment
• Emergency treatment of neonatal tetany
consists of iv injections 1-3 mg/kg of a 10%
solution of calcium gluconate (elemental calcium
9.3 mg/mL) at the rate of 0.5-1 mL/min and a
total dose not toexceed 20 mg of elemental
calcium/kg.
• Additionally, calcitriol should be given. The initial
dosage is 0.25 μg/24 hr; the maintenance
dosage ranges from 0.01-0.10 μg/kg/24 hr to a
maximum of 1-2 μg/24 hr.
• Calcitriol is supplied as an oral solution.

23. • Calcitriol has the advantages of rapid onset of
effect (1-4 days) and rapid reversal of
hypercalcemia after discontinuation in the event of
overdosage (calcium levels begin to fall in 3-4
days).
• An adequate intake of calcium should be ensured.
• Calcium gluconate or calcium glubionate- rarely
essential.
• Foods with high phosphorus content such as milk,
eggs, and cheese should be reduced in the diet.

24. • Pigmentation, lowering of blood pressure, or
weight loss can indicate adrenal insufficiency,
which requires specific treatment.
• Patients with autosomal dominant hypocalcemic
hypercalciuria can develop nephrocalcinosis and
renal impairment if treated with vitamin D.

25. Pseudohypoparathyroidism
(Albright Hereditary Osteodystrophy)

26. • The parathyroid glands are normal or
hyperplastic.
• Serum levels of immunoreactive PTH are
elevated even when the patient is hypocalcemic
and may be elevated when the patient is
normocalcemic.
• The genetic defects in the hormone receptor
adenylate cyclase system are classified into
various types depending on the phenotypic and
biochemical findings.

27. TYPE IA
• Genetic defect of the α subunit of the stimulatory
guanine nucleotide-binding protein (Gsα).
• Chromosome 20q13.2.
• Deficiency of the Gsα subunit is a generalized
cellular defect and accounts for the association
of other endocrine disorders.
• Autosomal dominant
• The paucity of father-to-son transmissions is
thought to be due to decreased fertility in males.

28. • Tetany is often the presenting sign.
• Short, stocky build and a round face.
• Brachydactyly with dimpling of the dorsum of the
hand is usually present.
• The 2nd
metacarpal is involved least often.
• Short and wide phalanges, bowing, exostoses,
and thickening of the calvaria.
• Subcutaneous calcium deposits and metaplastic
bone formation.
• Moderate mental retardation, calcification of the
basal ganglia, and lenticular cataracts.

29. • Pseudopseudohypoparathyroidism.
• There is some evidence to suggest that the Gsα
mutation is paternally transmitted in
pseudopseudohypoparathyroidism and
maternally transmitted in patients with type Ia
disease.

30. • Resistance to other G protein–coupled receptors
for thyroid-stimulating hormone (TSH),
gonadotropins, and glucagon can result in
various metabolic effects.
• Clinical hypothyroidism is uncommon.
• Moderately decreased levels of thyroxine and
increased levels of TSH in newborns.
• In adults, gonadal dysfunction is common.
• S. Ca2+ low, and phosphorus & ALP elevated.
• Attenuated response in urinary phosphate and
cAMP to human PTH.

31. TYPE IB
• Normal levels of G protein activity and a normal
phenotypic appearance.
• These patients have tissue-specific resistance to
PTH but not to other hormones.
• Serum levels of calcium, phosphorus, and
immunoreactive PTH are the same as those in
patients with type Ia PHP.
• Paternal uniparental isodisomy of chromosome
20q and resulting GNAS1 methylation.
• Loss of the maternal GNAS1 gene, leads to PTH
resistance in the proximal renal tubules, which
leads to impaired mineral ion homeostasis.

32. TYPE II
• Differs from type I in that the urinary excretion of
cAMP is elevated both in the basal state and
after stimulation with PTH but phosphaturia does
not increase.
• Phenotypically, patients are normal and
hypocalcemia is present.
• The defect appears to be distal to cAMP
because it is normally activated, but the cell is
unable to respond to the signal.

33. Hyperparathyroidism

34. • Primary hyperparathyroidism
• Secondary hyperparathyroidism

35. Etiology
• Childhood hyperparathyroidism is rare.
• Onset during childhood is usually the result of a
single benign adenoma.
• It usually becomes manifested after 10 yr of age.
• Autosomal dominant
• Multiple endocrine neoplasia (MEN)
• Hyperparathyroidism–jaw tumor syndrome
• Neonatal severe hyperparathyroidism (rare)

36. Neonatal severe hyperparathyroidism
• Symptoms develop shortly after birth
• Anorexia, irritability, lethargy, constipation, and
failure to thrive.
• Radiographs reveal subperiosteal bone
resorption, osteoporosis, and pathologic
fractures.

37. • Most cases have occurred in kindreds with the
clinical and biochemical features of familial
hypocalciuric hypercalcemia.
• Infants with neonatal severe
hyperparathyroidism may be homozygous or
heterozygous for the mutation in the Ca2+-
sensing receptor gene, whereas most persons
with 1 copy of this mutation exhibit autosomal
dominant familial hypocalciuric hypercalcemia.

38. MEN
• MEN type I- Autosomal dominant
• Hyperplasia or neoplasia of the
– endocrine pancreas (which secretes gastrin, insulin,
pancreatic polypeptide, and occasionally glucagon),
– anterior pituitary (which usually secretes prolactin),
– parathyroid glands.
• In most kindreds occurr only rarely in children
<18 yr of age.
• With appropriate DNA probes, it is possible to
detect carriers of the gene with 99% accuracy at
birth, avoiding unnecessary biochemical
screening programs.

39. Hyperparathyroidism–jaw tumor syndrome
• Autosomal dominant
• Parathyroid adenomas and fibro-osseous jaw
tumors.
• Affected patients can also have polycystic
kidney disease, renal hamartomas, and Wilms
tumor.
• Although the condition affects adults primarily, it
has been diagnosed as early as age 10 yr.

40. Transient neonatal hyperparathyroidism
• Occurs in few infants born to mothers with
hypoparathyroidism (idiopathic or surgical) or
with pseudohypoparathyroidism.

41. Clinical Manifestations
• Muscle weakness, fatigue, headache, anorexia,
abdominal pain, nausea, vomiting, constipation,
polydipsia, polyuria, weight loss, and fever.
• Nephrocalcinosis
• Renal calculi- renal colic and hematuria.
• Osseous changes can produce pain in the back
or extremities, disturbances of gait, genu
valgum, fractures, and tumors.
• Height can decrease from compression of
vertebrae; the patient can become bedridden.

42. • Abdominal pain is occasionally prominent and
may be associated with acute pancreatitis.
• Parathyroid crisis can occur, manifested by
serum calcium levels >15 mg/dL and
progressive oliguria, azotemia, stupor, and
coma.
• In infants, failure to thrive, poor feeding, and
hypotonia are common.

43. • Mental retardation, convulsions, and blindness
can occur as sequelae of long-standing
hypercalcemia.
• Psychiatric manifestations include depression,
confusion, dementia, stupor, and psychosis.

44. Laboratory Findings
• S. Ca2+ elevated
• The hypercalcemia is more severe in infants with
parathyroid hyperplasia; concentrations ranging
from 15 to 20 mg/dL are common, and values as
high as 30 mg/dL have been reported.
• Even when the total serum calcium level is
borderline or only slightly elevated, ionized
calcium levels are often increased.
• Serum phosphorus- low
• Serum magnesium- low

45. • Urine- low and fixed specific gravity
• Serum levels of nonprotein nitrogen and uric
acid may be elevated.
• In patients with adenomas who have skeletal
involvement, serum phosphatase levels are
elevated, but in infants with hyperplasia the
levels of alkaline phosphatase may be normal
even when there is extensive involvement of
bone.

46. • PTH are elevated
• Calcitonin levels are normal- Acute
hypercalcemia can stimulate calcitonin release,
but with prolonged hypercalcemia,
hypercalcitoninemia does not occur.

47. • The most consistent and characteristic
radiographic finding is resorption of
subperiosteal bone, best seen along the
margins of the phalanges of the hands.
• Skull- gross trabeculation or a granular
appearance resulting from focal rarefaction;
• Lamina dura may be absent.
• In more advanced disease, there may be
generalized rarefaction, cysts, tumors, fractures,
and deformities.

48. Treatment
• Surgical exploration is indicated in all instances.
• Most neonates with severe hypercalcemia
require total parathyroidectomy.
• A portion of a parathyroid gland may be
autografted into the forearm.
• The patient should be carefully observed
postoperatively for the development of
hypocalcemia and tetany; intravenous
administration of calcium gluconate may be
required for a few days.

49. • The prognosis is good if the disease is
recognized early.
• When extensive osseous lesions are present,
deformities may be permanent.