Pediatric Hyperparathyroidism Clinical Presentation

Updated: Apr 17, 2017
  • Author: Edna E Mancilla, MD; Chief Editor: Sasigarn A Bowden, MD  more...
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The main causes of hyperparathyroidism by age groups are detailed in Table 1. Homozygous inactivating CASR mutations lead to NSHPT, while heterozygous mutations are observed mainly in the milder form, Familial Hypocalciuric Hypercalcemia (FHH), although cases of NSHPT with heterozygous mutations have been reported. [14]   FHH is inherited in an autosomal dominant manner, but may be sporadic. Additionally, mutations in the G protein subunit α 1 and AP2S1 gene have recently been found to cause FHH. [15, 16]   FHH manifests with mild hypercalcemia  associated with hypocalciuria, most often not requiring specific treatment.

In older children and adolescents primary hyperparathyroidism is most often caused by isolated sporadic parathyroid adenomas (80-92%). [17] The remaining are due to multiglandular parathyroid hyperplasia observed in familial endocrine neoplastic syndromes , in which cases a family history of endocrine tumors  with an autosomal dominant pattern of inheritance often exists. Multiple Endocrine Neoplasia type 1 is caused by a mutation in the gene MEN1 which encodes menin, a tumor suppressor protein. Hyperparathyroidism is the presenting sign in 95% of patients with MEN1, while pancreatic and pituitary tumors develop in 40 and 30% of cases respectively. [9] MEN 2A is caused by mutations in the c-ret proto-oncogene  (RET ) which encodes a tyrosine kinase receptor. MEN 2A presents with medullary thyroid carcinoma associated with hyperparathyroidism (20%) and pheochromocytoma (50%). MEN 4 is caused by mutations in CDKN1B, a cyclin dependent kinase inhibitor, and has been diagnosed in a small percentage of patients with the tumors associated with MEN1 in addition to adrenal, gonadal and thyroid tumors.  Hyperparathyroidism Jaw Tumor syndrome is caused by mutations in cell division cycle 73 gene (CDC73) which codes for parafibromin, a nuclear protein thought to be a tumor suppressor gene.  In this syndrome, osseous fibromas of the jaw are associated with parathyroid adenomas or carcinomas, and renal and uterine tumors may also be found. [9]  In general, parathyroid carcinoma is very rare in children with 11 cases reported in the English literature in the past 41 years. [11]

Table 1. Causes of hyperparathyroidism (Open Table in a new window)




1.      Neonate/Infant

  • Primary

             - Familial hypocalciuric hypercalcemia

Heterozygous inactivating CASR mutations


             - Neonatal severe hyperparathyroidism

Homozygous inactivating CASR mutations


  • Secondary

             - Maternal hypoparathyroidism     


             - Maternal pseudohypoparathyroidism


             - Maternal Vitamin D deficiency


2.      Child/adolescent

  • Primary

             - Sporadic adenomas


             - Familial


                    * Familial hypocalciuric   

                       hypercalcemia (FHH)



                    * Multiple Endocrine Neoplasia

                       type 1 (MEN1)



                    * Multiple Endocrine Neoplasia

                       type 2a



                    * Multiple Endocrine Neoplasia

                       type 4



                    * Familial hyperparathyroidism 

                       jaw tumor syndrome (HRPT2)

CDC73 145001



             - Autoantibodies to the CASR

  • Secondary

             - Renal failure/post renal transplant


             - Chronic hyperphosphatemia


             - Vitamin D deficiency


                    * Nutritional


                    * Malabsorption


              -Vitamin D dependent rickets

                       type 1 VDDR1

CYP27B1 264700




              - Vitamin D dependent rickets    

                       type 2 VDDR2

Vitamin D receptor  277440




              -Other causes of hypocalcemia


                     Poor intake




NSHPT represents a severe form of hyperparathyroidism observed in neonates, with a high mortality rate if untreated.  Symptoms include dehydration secondary to polyuria, feeding difficulties and vomiting, altered mental status, hypotonia, respiratory distress and fractures. FHH is milder, often asymptomatic. [18]

Unlike adults, the majority of children and adolescents with primary hyperparathyroidism are symptomatic, with symptoms secondary to hypercalcemia or the effects of PTH on target organs. Hypercalcemia affects cell depolarization leading to gastrointestinal, neurologic and cardiac signs and symptoms.  Gastrointestinal symptoms are common, and are partly due to increased gastric acid secretion. These symptoms include abdominal pain, nausea, anorexia, constipation and vomiting. Polyuria is caused by the direct effects of hypercalciuria on the nephron and by the stimulation of the CASR in the collecting tubules leading to decreased Antidiuretic Hormone action. Headache, depression, fatigue and anxiety are amongst the most frequent neurological symptoms.  Renal calculi, hematuria, dehydration, bone pain and fractures are presenting symptoms in more than 50% of pediatric cases. [4] Bradycardia and heart block may be observed with severe hypercalcemia.   In cases where hyperparathyroidism is part of a multiglandular syndrome there may be a history of symptoms associated with other endocrine tumors, and a positive family history for similar tumors. The proportion of asymptomatic pediatric patients diagnosed by the  incidental finding of hypercalcemia during routine blood chemistry  is lower than that reported in adults, with a range of 14 to 25% in recent pediatric series.



Physical Examination

Physical Exam


See the list below:

  • Depressed mood, anxiety and altered mental status. 
  • Poor weight gain and failure to thrive in younger children and infants
  • Bradycardia, with or without irregular heartbeat
  • Signs of dehydration such as dry mucous membranes, prolonged capillary refill, tenting of skin.
  • Abdominal pain due to increased gastric acid secretion, constipation, peptic ulcers or acute pancreatitis.
  • Hypotonia
  • Flank pain due to renal calculi.
  • Signs of fractures such as bone pain and deformities are more common in neonates with NSHPT



Acute complications if untreated are those of hypercalcemia.

Chronic complications:

Failure to thrive

Low Bone Mineral Density


Nephrolithiasis or nephrocalcinosis

Renal failure