Pseudohypoparathyroidism Treatment & Management
- Author: Mini R Abraham, MD; Chief Editor: George T Griffing, MD more...
The goals of therapy are to maintain serum total and ionized calcium levels within the reference range to avoid hypercalciuria and to suppress PTH levels to normal. This is important because elevated PTH levels in patients with PHP can cause increased bone remodeling and lead to hyperparathyroid bone disease.
All patients with severe symptomatic hypocalcemia should be initially treated with intravenous calcium. Administration of oral calcium and 1alpha-hydroxylated vitamin D metabolites, such as calcitriol, remains the mainstay of treatment and should be initiated in every patient with a diagnosis of PHP.
In adults, infuse approximately 100 mg of elemental calcium (either calcium chloride or calcium gluconate) over 10-20 minutes. If this measure does not alleviate the clinical manifestation, 100 mg/h of elemental calcium can be infused (in adults), with close monitoring of calcium levels. Do not rapidly infuse calcium, because of the possible adverse effects of cardiac conduction defects; cardiac monitoring may help to guide therapy.
The 2 most readily available formulations for parenteral use are calcium chloride and calcium gluconate; a 10-mL ampule of 10% calcium chloride contains 360 mg of elemental calcium, and a 10-mL ampule of 10% calcium gluconate contains 93 mg of elemental calcium.
For neonates, infants, and children, the recommended initial dose is 0.5-1 mL/kg of 10% calcium gluconate administered over 5 minutes.
Pseudohypoparathyroidism type 1B patients could develop tertiary hyperparathyroidism and/or hyperparathyroid bone disease. Therefore, it is important to treat them with sufficient doses of calcium and vitamin D to maintain serum calcium and PTH levels within or as close to the normal range as possible.
Rarely, extraskeletal osteomas require surgical removal to relieve pressure symptoms. Parathyroidectomy is the treatment of choice in patients with tertiary hyperparathyroidism.
Monitor therapy through regular serum and urinary calcium measurements. Exercise caution to avoid renal or hypercalcemic complications. In addition, monitor serum PTH levels with a goal of maintaining serum PTH levels within the reference range.
Bastepe M. The GNAS locus and pseudohypoparathyroidism. Adv Exp Med Biol. 2008. 626:27-40. [Medline].
Nakamura Y, Matsumoto T, Tamakoshi A, et al. Prevalence of idiopathic hypoparathyroidism and pseudohypoparathyroidism in Japan. J Epidemiol. 2000 Jan. 10(1):29-33. [Medline].
Davies SJ, Hughes HE. Imprinting in Albright's hereditary osteodystrophy. J Med Genet. 1993 Feb. 30(2):101-3. [Medline].
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. 1998 Sep 29. 95(20):11798-803. [Medline].
Wu WI, Schwindinger WF, Aparicio LF, Levine MA. Selective resistance to parathyroid hormone caused by a novel uncoupling mutation in the carboxyl terminus of G alpha(s). A cause of pseudohypoparathyroidism type Ib. J Biol Chem. 2001 Jan 5. 276(1):165-71. [Medline].
Bliek J, Verde G, Callaway J, et al. Hypomethylation at multiple maternally methylated imprinted regions including PLAGL1 and GNAS loci in Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2009 May. 17(5):611-9. [Medline].
Long DN, McGuire S, Levine MA, et al. Body mass index differences in pseudohypoparathyroidism type 1a versus pseudopseudohypoparathyroidism may implicate paternal imprinting of Galpha(s) in the development of human obesity. J Clin Endocrinol Metab. 2007 Mar. 92(3):1073-9. [Medline]. [Full Text].
Shalitin S, Davidovits M, Lazar L, et al. Clinical heterogeneity of pseudohypoparathyroidism: from hyper- to hypocalcemia. Horm Res. 2008. 70(3):137-44. [Medline].
Balavoine AS, Ladsous M, Velayoudom FL, et al. Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH. Eur J Endocrinol. 2008 Oct. 159(4):431-7. [Medline].
Mantovani G, Bondioni S, Linglart A, Maghnie M, Cisternino M, Corbetta S. Genetic analysis and evaluation of resistance to thyrotropin and growth hormone-releasing hormone in pseudohypoparathyroidism type ib. J Clin Endocrinol Metab. 2007 Sep. 92(9):3738-42. [Medline].
Vlaeminck-Guillem V, D'herbomez M, Pigny P, Fayard A, Bauters C, Decoulx M, et al. Pseudohypoparathyroidism Ia and hypercalcitoninemia. J Clin Endocrinol Metab. 2001 Jul. 86 (7):3091-6. [Medline].
Landreth H, Malow BA, Shoemaker AH. Increased Prevalence of Sleep Apnea in Children with Pseudohypoparathyroidism Type 1a. Horm Res Paediatr. 2015. 84 (1):1-5. [Medline].
Mahmud FH, Linglart A, Bastepe M, et al. Molecular diagnosis of pseudohypoparathyroidism type Ib in a family with presumed paroxysmal dyskinesia. Pediatrics. 2005 Feb. 115(2):e242-4. [Medline].
Freson K, Izzi B, Labarque V, et al. GNAS defects identified by stimulatory G protein alpha-subunit signalling studies in platelets. J Clin Endocrinol Metab. 2008 Dec. 93(12):4851-9. [Medline].
Todorova-Koteva K, Wood K, Imam S, Jaume JC. Screening for parathyroid hormone resistance in patients with nonphenotypically evident pseudohypoparathyroidism. Endocr Pract. 2012 Nov-Dec. 18(6):864-9. [Medline].
Weinhaeusel A, Thiele S, Hofner M, et al. PCR-based analysis of differentially methylated regions of GNAS enables convenient diagnostic testing of pseudohypoparathyroidism type Ib. Clin Chem. 2008 Sep. 54(9):1537-45. [Medline].
Neary NM, El-Maouche D, Hopkins R, Libutti SK, Moses AM, Weinstein LS. Development and treatment of tertiary hyperparathyroidism in patients with pseudohypoparathyroidism type 1B. J Clin Endocrinol Metab. 2012 Sep. 97(9):3025-30. [Medline]. [Full Text].
Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L. Pseudohypoparathyroidism - epidemiology, mortality and risk of complications. Clin Endocrinol (Oxf). 2015 Sep 21. [Medline].
Ritter C, Göbel CH, Liebig T, Kaminksy E, Fink GR, Lehmann HC. An epigenetic cause of seizures and brain calcification: pseudohypoparathyroidism. Lancet. 2015 May 2. 385 (9979):1802. [Medline].