Pseudohypoparathyroidism natural history, complications and prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mazia Fatima, MBBS [2]

Overview

Patients with pseudohypoparathyroidism type Ia have an increased rate of other endocrine abnormalities (such as hypothyroidism and hypogonadism). Complications of hypocalcemia associated with pseudohypoparathyroidism may include seizures and other endocrine problems, leading to decreased sexual drive and delayed sexual development, fatigue, and increased weight.

Natural History

If left untreated, patients with pseudohypoparathyroidism type1a, type 1c and pseudopseudohypoparathyroidism present by the second decade of life with characteristic physical features of Albright’s hereditary osteodystrophy like:
- Subcutaneous ossifications
- Shortening of third, fourth, and fifth metacarpals and metatarsals
- Round face
- Obesity
- Frontal bossing
- Dental hypoplasia
If left untreated, pseudohypoparathyroidism type 1b patients at an increased risk of developing hyperparathyroidism and hyperparathyroid bone disease as a result of long-term elevation in parathyroid hormone.

Complications

Complications that can develop as a result of pseudohypoparathyroidism are:^[1]^[2]^[3]^[4]

Seizures (children)
Hypothyroidism due to associated resistance to thyrotropin
Gonadotropin
Growth hormone releasing hormone(GHRH) resistance
Patients may develop hypocalcemia resulting in:
- Paresthesias
- Muscular cramping
- Tetany
- Carpopedal spasm
Patients with pseudohypoparathyroidism type Ia have an increased rate of other endocrine abnormalities (such as hypothyroidism and hypogonadism)

Pseudohypoparathyroidism type 1b patients are at risk of developing tertiary hyperparathyroidism and hyperparathyroid bone disease.

Osteopenia and rickets in peudohypoparathyroidism type 1a are associated with variable osteoclast responsiveness to parathyroid hormone.

Prognosis

In few cases of pseudohypoparathyroidism, calcium homeostasis adapts to parathyroid hormone resistance resulting in resolution of hypocalcemia.
Patients who do not adapt to parathyroid hormone resistance are managed with lifelong calcium supplementation.
Long term levothyroxine is used in patients with associated hypothyroidism.

References

↑ Shalitin S, Davidovits M, Lazar L, Weintrob N (2008). “Clinical heterogeneity of pseudohypoparathyroidism: from hyper- to hypocalcemia”. Horm. Res. 70 (3): 137–44. doi:10.1159/000137658. PMID 18663313.
↑ Adachi M, Muroya K, Asakura Y, Kondoh Y, Ishihara J, Hasegawa T (2009). “Ectopic calcification as discernible manifestation in neonates with pseudohypoparathyroidism type 1a”. Int J Endocrinol. 2009: 931057. doi:10.1155/2009/931057. PMC 2778176. PMID 20011056.
↑ Neary NM, El-Maouche D, Hopkins R, Libutti SK, Moses AM, Weinstein LS (2012). “Development and treatment of tertiary hyperparathyroidism in patients with pseudohypoparathyroidism type 1B”. J. Clin. Endocrinol. Metab. 97 (9): 3025–30. doi:10.1210/jc.2012-1655. PMC 3431579. PMID 22736772.
↑ Balavoine AS, Ladsous M, Velayoudom FL, Vlaeminck V, Cardot-Bauters C, d’Herbomez M, Wemeau JL (2008). “Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH”. Eur. J. Endocrinol. 159 (4): 431–7. doi:10.1530/EJE-08-0111. PMID 18805917.

Overview