eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Hypoparathyroidism: Differential Diagnoses & Workup

Author: James CM Chan, MD, Professor of Pediatrics, University of Vermont College of Medicine; Director of Research, The Barbara Bush Children's Hospital, Maine Medical Center
Contributor Information and Disclosures

Updated: Sep 17, 2009

Differential Diagnoses

Hypomagnesemia

Other Problems to Be Considered

Vitamin D deficiency
Hyperphosphatemia
Hypoproteinemia
Pancreatitis
Drugs - Citrate, furosemide, calcitonin, mithramycin
Calcium-sensing receptor mutations (see Causes)

Workup

Laboratory Studies

  • Total and ionized serum calcium: In hypoparathyroidism and pseudophypoparathyroidism (PHP), total and ionized calcium levels are low.
  • Serum phosphate: Serum phosphate levels are elevated in hypoparathyroidism and PHP, although they can be within the reference range.
  • Serum magnesium: Serum magnesium levels are obtained to rule out hypomagnesemia as a cause of hypocalcemia. Magnesium levels are within the reference range in hypoparathyroidism and PHP.
  • Intact parathyroid hormone (iPTH): Obtain iPTH at the time of hypocalcemia. Nomograms have been developed for the interpretation of serum iPTH concentration with respect serum calcium. In hypoparathyroidism, iPTH is low. An iPTH that falls within the reference range must be interpreted with caution. The value might be considered low in the face of hypocalcemia. In PHP, iPTH is elevated.
  • BUN and creatinine levels: BUN and creatinine concentrations are obtained to assess renal function. These test results are normal in hypoparathyroidism and PHP.
  • 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D: 25-Hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations are obtained to rule out a vitamin D–deficient or vitamin D–resistant state as the etiology of hypocalcemia. 25-Hydroxyvitamin D levels are within the reference range in hypoparathyroidism and PHP. 1,25-Dihydroxyvitamin D levels are expected to be low in hypoparathyroid states because of lack of PTH-stimulated 1-alpha-hydroxylase activity. Elevated 1,25-dihydroxyvitamin D concentrations have been documented in PHP, but the mechanism remains unclear.
  • Urine calcium and creatinine ratio: Urine calcium is elevated in PTH-resistant and PTH-deficient states and particularly elevated in calcium-sensing receptor mutations.
  • Thyroid-stimulating hormone (TSH), thyroxine, and thyroid antibodies
  • Thyroid studies: If an autoimmune process is suspected as the etiology of hypoparathyroidism, thyroid studies may uncover a concomitant hypothyroid state.
  • Adrenocorticotropic hormone (ACTH) and adrenal antibodies: If an autoimmune process is suspected, concomitant adrenal insufficiency can be revealed by an elevated ACTH level, and adrenal antibodies may be present.

Imaging Studies

  • Chest radiography: Thymic aplasia is associated with the 22q11 deletion syndrome and can be assessed with chest radiography.
  • Echocardiography: An infant with a murmur and in whom hypoparathyroidism is suggested should have echocardiography performed to assess for conotruncal lesions that are associated with the 22q11 deletion syndrome.
  • Renal ultrasonography: Treatment of hypoparathyroidism can lead to nephrocalcinosis as a result of calciuria. Baseline renal ultrasonography with initial treatment should be performed.
  • Hand and wrist radiography: Brachymetacarpals are a feature of Albright hereditary osteodystrophy (AHO) phenotype and can aid in the diagnosis of PHP Ia.
  • Brain MRI: Basal ganglia calcifications suggest that a long-standing calcium disorder is present and are more common with PHP.

Other Tests

  • Electrocardiography: A prolonged QTc interval is found with hypocalcemia and resolves with correction of serum calcium.
  • ACTH stimulation testing: Adrenal insufficiency can be life threatening. If APS I is suggested, an ACTH stimulation study should be performed to assess adrenal function (if basal ACTH levels are elevated).
  • Thyrotropin-releasing hormone stimulation testing: PHP Ia is associated with generalized hormone resistance. Hypothyroidism may be subtle and may only be detected with a thyrotropin-releasing hormone (TRH) stimulation study.
  • Genetic studies, when applicable
  • In neonates, a fluorescence in situ hybridization for the chromosome band 22q11 deletion

More on Hypoparathyroidism

Overview: Hypoparathyroidism
Differential Diagnoses & Workup: Hypoparathyroidism
Treatment & Medication: Hypoparathyroidism
Follow-up: Hypoparathyroidism
Multimedia: Hypoparathyroidism
References
[ CLOSE WINDOW ]

References

  1. Roth KS, Ward RJ, Chan JCM, Sarafoglou K. Disorders of calcium, phosphate, and bone metabolism. In: Sarafoglou K. Hoffman GF, Roth KS. Pediatric endocrinology and inborn errors of metabolism. ed. New York, NY: McGraw Hill; 2009:619-64.

  2. Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis- ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med. Jun 28 1990;322(26):1829-36. [Medline].

  3. Arnold A, Horst SA, Gardella TJ, et al. Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism. J Clin Invest. Oct 1990;86(4):1084-7. [Medline]. [Full Text].

  4. Chattopadhyay N, Mithal A, Brown EM. The calcium-sensing receptor: a window into the physiology and pathophysiology of mineral ion metabolism [published erratum appears in Endocr Rev 1996 Oct;17(5):517]. Endocr Rev. Aug 1996;17(4):289-307. [Medline]. [Full Text].

  5. Chinnery PF, Turnbull DM. Mitochondrial medicine. QJM. Nov 1997;90(11):657-67. [Medline]. [Full Text].

  6. Farfel Z, Bourne HR, Iiri T. The expanding spectrum of G protein diseases. N Engl J Med. Apr 1 1999;340(13):1012-20. [Medline].

  7. Fischer JA, Egert F, Werder E, Born W. An inherited mutation associated with functional deficiency of the alpha-subunit of the guanine nucleotide-binding protein Gs in pseudo- and pseudopseudohypoparathyroidism. J Clin Endocrinol Metab. Mar 1998;83(3):935-8. [Medline]. [Full Text].

  8. Hasegawa T, Hasegawa Y, Aso T, et al. HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia) associated with del(10)(p13). Am J Med Genet. Dec 31 1997;73(4):416-8. [Medline].

  9. Hayward BE, Moran V, Strain L, Bonthron DT. Bidirectional imprinting of a single gene: GNAS1 encodes maternally, paternally, and biallelically derived proteins. Proc Natl Acad Sci U S A. Dec 22 1998;95(26):15475-80. [Medline]. [Full Text].

  10. Juppner H, Schipani E, Bastepe M, et al. The gene responsible for pseudohypoparathyroidism type Ib is paternally imprinted and maps in four unrelated kindreds to chromosome 20q13.3. Proc Natl Acad Sci U S A. Sep 29 1998;95(20):11798-803. [Medline]. [Full Text].

  11. Levine MA. Pseudohypoparathyroidism: from bedside to bench and back. J Bone Miner Res. Aug 1999;14(8):1255-60. [Medline].

  12. Nakamoto JM, Sandstrom AT, Brickman AS, et al. Pseudohypoparathyroidism type Ia from maternal but not paternal transmission of a Gsalpha gene mutation. Am J Med Genet. May 26 1998;77(4):261-7. [Medline].

  13. Pearce SH, Williamson C, Kifor O, et al. A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor. N Engl J Med. Oct 10 1996;335(15):1115-22. [Medline].

  14. Perheentupa J. Autoimmune polyendocrinopathy--candidiasis--ectodermal dystrophy (APECED). Horm Metab Res. Jul 1996;28(7):353-6. [Medline].

  15. Pollak MR, Brown EM, Estep HL, et al. Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation. Nat Genet. Nov 1994;8(3):303-7. [Medline].

  16. Sticht H, Hashemolhosseini S. A common structural mechanism underlying GCMB mutations that cause hypoparathyroidism. Med Hypotheses. May 11 2006;[Medline].

  17. Sunthornthepvarakul T, Churesigaew S, Ngowngarmratana S. A novel mutation of the signal peptide of the preproparathyroid hormone gene associated with autosomal recessive familial isolated hypoparathyroidism. J Clin Endocrinol Metab. Oct 1999;84(10):3792-6. [Medline]. [Full Text].

  18. Yamamoto M, Akatsu T, Nagase T, Ogata E. Comparison of hypocalcemic hypercalciuria between patients with idiopathic hypoparathyroidism and those with gain-of-function mutations in the calcium-sensing receptor: is it possible to differentiate the two disorders?. J Clin Endocrinol Metab. Dec 2000;85(12):4583-91. [Medline]. [Full Text].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

hypoparathyroidism, hypocalcemia, pseudohypoparathyroidism, PHP, pseudopseudohypoparathyroidism, PPHP, polyglandular autoimmune endocrinopathy, DiGeorge syndrome, Barakat syndrome, Kenny-Caffey syndrome, Albright hereditary osteodystrophy, parathyroid insufficiency, familial hypercalciuric hypocalcemia, familial isolated hypoparathyroidism, calcium-sensing receptor hypocalcemia, Kearns-Sayre syndrome, Pearson marrow pancreas, laryngospasm, syncope, seizure, tetany, muscle aches, facial twitching, carpopedal spasm, tetralogy of Fallot, truncus arteriosus, Albright hereditary osteodystrophy, AHO, obesity, treatment, diagnosis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

James CM Chan, MD, Professor of Pediatrics, University of Vermont College of Medicine; Director of Research, The Barbara Bush Children's Hospital, Maine Medical Center
James CM Chan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association of University Professors, American Chemical Society, American Heart Association, American Medical Association, American Physiological Society, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, New York Academy of Sciences, Society for Experimental Biology and Medicine, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Thomas A Wilson, MD, Professor of Clinical Pediatrics, Department of Pediatrics; Director of Pediatric Endocrinology, Division of Pediatric Endocrinology, Department of Pediatrics, State University of New York at Stony Brook
Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London), Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece
George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.