Hyperparathyroidism in children is uncommon and usually results from a single benign adenoma. It involves excessive production of parathyroid hormone (PTH) which increases calcium levels and can cause symptoms like weakness, nausea, and bone pain. Diagnosis involves lab tests showing high calcium and PTH levels. Primary hyperparathyroidism is typically treated by surgically removing the adenoma, while secondary causes related to kidney disease are managed medically. Without treatment, effects on bones can cause fractures and deformities.

1. Hyperparathyroidism in children
Dr Joyce MWATONOKA
Resident, Pediatrics and Child Health

2. Introduction
• Excessive production of PTH
• Primary hyperparathyroidism; defect of the
parathyroid glands such as an adenoma (80%) or
hyperplasia, rarely carcinoma
• Secondary hyperparathyroidism; compensatory,
usually aimed at correcting hypocalcemic states
of diverse origins eg; CKD, Vit D deficiency,
malabsorption
• Tertialy hyperparathyroidism; hyperlasia due to
intense and protracted stimulation

3. Epidemiology
• Childhood hyperparathyroidism is uncommon
• Estimated incidence in children is 1 per 200-
300,000
• Prevalence is 2-5 in 100,000
• Higher predominance in adolescence,
although still very low compared to adults

4. PTH physiology
• When serum levels of calcium fall, the signal is
transduced through the calcium-sensing
receptor, and secretion of PTH increases
• PTH stimulates activity of 1α-hydroxylase in
the kidney, enhancing production of 1,25-
dihydroxycholecalciferol
• Which induces synthesis of a calcium-binding
protein (calbindin-D) in the intestinal mucosa,
with resultant absorption of calcium

5. Cont…
• PTH also mobilizes calcium by directly
enhancing bone resorption, an effect that
requires 1,25(OH)2D3

6. Etiology
• Onset during childhood is usually the result of a
single benign adenoma (Familial isolated
hyperparathyroidism)
• It usually becomes manifested after 10 yr of age
• AD. Mostly affect adults, but children have been
involved in approximately 30% of the pedigrees
• Can be caused by mutations in the MEN1, CDC73
or CASR gene

7. Cont…
• In other kindreds, hyperparathyroidism occurs
as part of the constellation known as the
multiple endocrine neoplasia (MEN)
syndromes or of the hyperparathyroidism–
jaw tumor syndrome

8. MEN type I
• Is an AD disorder characterized by hyperplasia
or neoplasia of the endocrine pancreas, the
anterior pituitary, and the parathyroid glands
• Hyperparathyroidism is usually the presenting
manifestation, with a prevalence approaching
100% by 50yr
• Rarely occurs in children <18 yr

9. Cont…

10. Hyperparathyroidism–jaw tumor
syndrome
• It is an AD disorder characterized by
parathyroid adenomas and fibro-osseous jaw
tumors (osteitis fibrosa cystica)
• 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

12. Familial hypocalciuric hypercalcemia
(FHH)
• Rare benign, genetic condition, AD
• Loss of function mutations in the CASR gene
• Generally asymptomatic
• Low urinary calcium (<0.02 mmol/L)
• Increased serum calcium levels (usually 10.5-
12mg/dl), mild to moderate
• Hypermagnesemia, hypophosphatemia
• PTH, usually normal or mild elevated

13. Neonatal severe hyperparathyroidism
• It is a rare disorder
• May be homozygous or heterozygous for the
mutation in the Ca2+-sensing receptor gene,
whereas most persons with 1 copy of this
mutation exhibit AD familial hypocalciuric
hypercalcemia
• Histologically, the parathyroid glands show
diffuse hyperplasia

14. Cont…
• Sxs develop shortly after birth and consist of
anorexia, irritability, lethargy, hypotonia,
constipation, and failure to thrive
• Radiographs reveal subperiosteal bone
resorption, osteoporosis, and pathologic
fractures
• Sxs may be mild, resolving without treatment,
or can have a rapidly fatal course if dx and
treatment are delayed

15. Transient neonatal
hyperparathyroidism
• Occurr in few infants born to mothers with
hypoparathyroidism (idiopathic/surgical) or with
pseudohypoparathyroidism
• In each case, the maternal disorder had been
undiagnosed or inadequately treated during
pregnancy
• Due to chronic intrauterine exposure to
hypocalcemia with resultant hyperplasia of the
fetal parathyroid glands. In the newborn,
manifestations involve the bones primarily, and
healing occurs between 4 - 7mo of age

16. Cont…
• In pseudohypoparathyroidism, PTH levels are
elevated because a mutation in the Gsα
protein interferes with response to PTH
• Hence resistance to PTH
• Elevated PTH, hyperphosphatemia, and
hypocalcemia with normal Vit D levels and
renal function

17. Secondary hyperparathyroidism
• Early in CKD, hyperphosphatemia results in a
reciprocal fall in the calcium concentration
with a consequent increase in PTH
• But in advanced stages of renal failure,
production of 1,25(OH)2D3 is also decreased,
leading to worsening hypocalcemia and
further stimulation of PTH

18. Clinical manifestations (of
hypercalcemia)
• Muscle weakness, fatigue, headache,
anorexia, abdominal pain (pancreatitis,
constipation), nausea, vomiting, constipation,
polydipsia, polyuria, weight loss, and fever
• CVS; heart block, short QT interval,
arrhythmias
• Renal; polyuria, nephrogenic DI, AKI, CKD,
nephrocalcinosis

19. Bones, stones, moans & psychiatric
overtone
• Bones; fractures, weakness, bone pain
• Stones; nephrolithiasis
• Groans/moans; abdominal cramping, nausea,
ileus, constipation
• Psychiatric overtone; (neuronal hypoactivity)
hyporeflexia, depressed mood, confusion,
lethargy, nephrogenic diabetes insipidus -
dehydration
-Ca is a competitive inhibitor of ADH

20. Laboratory findings
Primary
• Increased serum PTH levels
• Elevated total serum calcium
and ionized calcium levels
• Increase in urinary calcium
excretion
• Serum phosphorus level is
reduced to approximately 3
mg/dL or less
• Mild hyperchloremic acidosis
• Measure Vit D levels
Secondary
• Increased serum PTH levels
• Normal or low calcum levels
• Vitamin D deficincy
• Underlying renal failure
(CKD)

22. Cont…
• Adenomas with skeletal involvement, serum
ALP levels are elevated, but in hyperplasia the
levels of ALP may be normal even when there
is extensive involvement of bone
• Calcitonin levels are normal; Acute
hypercalcemia can stimulate calcitonin
release, but with prolonged hypercalcemia,
hypercalcitoninemia does not occur

23. Radiography
• Subperiosteal bone
resorption, best
seen along the
margins of the
phalanges of the
hands
(laterally/along the
radial)
• Pathognomonic for
hyperparathyroidism

24. Cont…
• Distal clavicular
resorption

25. Cont…
• Salt and pepper
appearance
-multiple punched out
lesions on the skull
• Classical in primary
hyperthyroidism

26. Cont…
• Rugger jersey sign
-sclerotic superior
and inferior
endplates
• Diagnostic for
osteoslerosis ass/c
secondary
hyperparathyroidism

27. Cont…
• In more advanced disease, there may be
generalized rarefaction, cysts, tumors,
fractures, and deformities
• Approximately 10% of patients have
radiographic signs of rickets
• Abdominal X-ray can reveal renal calculi or
nephrocalcinosis

28. Cont…
• Parathyroid maging;
-USS
-CT
-MRI
-Radioisotope scanning using 99mTc-sestamibi
• Bone densitrometry (DXA)

29. Other causes of hypercalcemia
• Endocrine
• Idiopathic infantile
hypercalcemia
• Vitamin D (intoxication,
subcutaneous fat
necross)
• Drugs; thiazide
diuretics, lithium
• Miscellaneous;
hypophospatemia,
vitamin A intoxication,
blue-diaper syndrome
• Malignancy; bone
metastases, breast,
lung, bone cancer
• Granulomatous d’ses;
TB, sarcoidosis

30. Treatment
• Primary; Adenoma – parathyroidectomy
• Secondary; medical management, Vit D
replacement, phosphate restriction/binding
agents
• Tertiary; total/subtotal parathyoidectomy
• Postoperatively observe for hypocalcemia and
tetany; IV calcium gluconate may be required for
a few days. Calcium level gradually returns to
normal, a diet high in calcium and phosphorus
must be maintained for several months

31. Cont…
• Fluids; 0.9% NS
• Loop diuretics
• Bisphosphonates; alendronate, ibandronate
(reduce osteoclast activity)
-Second line; Long term side effect-interferes
with bone turnover. Short term; hypocalcemia
• IV calcitonin for more rapid reduction
-side effect, hypocalcemia
• Dialysis; severe hypercalcemia >18mg/dl

32. Cont…
• Corticosteroids lower the serum calcium level
to normal in patients with hypercalcemia from
other causes but generally do not affect the
calcium level in patients with
hyperparathyroidism

33. Treating other causes of
hypercalcemia
• Most neonates with severe hypercalcemia
require total parathyroidectomy; less-severe
hypercalcemia remits spontaneously in others
-calcimimetics
• Familial hypercalciuric hypercalcemia; loop
diuretics
• Malignancy (low PTH, high Ca); full work up
including assay for PTHrP, ALP, calcitriol, femur
xray/MM work up)

34. Px
• The prognosis is good if the disease is
recognized early and there is appropriate
surgical treatment
• When extensive osseous lesions are present,
deformities may be permanent
• A search for other affected family members is
indicated