The pseudosPseudo from the greek – false or lying

Samantha Harrison MBBS 3 KCL

Pseudohypoparathyroidism Definition:

Characterised by a peripheral resistance to parathyroid hormone rather than a deficiency

Hypocalcaemia, hyperphosphataemia, raised serum PTH

Three Types: 1a, 1b, 2 Epidemiology:

F:M ratio – 2:1 Only prevalence study – Japan (1998) – 3.4 cases

per million Any age can be affected

Etiology Collection of Autosomal Dominant

inherited genetic conditions All heterozygous Haploinsufficiency of GNAS1 – only 1

copy of the normal protein. It is not fatal but cannot continue normal functioning

Pseudohypoparathyroidism: Type 1a Signs and Symptoms

Type 1a Short 4th and 5th metacarpals, round face, short

stature, calcium deposits under the skin, dimples, stocky habitus, developmental delay, dental hypoplasia, soft tissue calcification/ossification

Also called Albright hereditary dystrophy Associated with TSH resistance, hypogonadism,

females often suffer impaired fertility, oligomenorrhea, delayed puberty, male – infertility

Pathophysiology Molecular defect in gene (GNAS1) GNAS1 encodes the alpha subunit of the stimulatory G

protein (Gsa)

Gsa is involved with: thyrotropin, antidiuretic hormone, the gonadotropins, glucagon, adrenocorticotropin, and growth hormone–releasing hormone. Also can affect senses

Type 1b Pathophysiology of Type 1b is by the

same mechanism (GNAS1) leading to Gsa defect.

Characterised by only renal resistance to parathyroid hormone, otherwise endocrinologically normal

Sufferers are variably affected Paternal imprinting.

Type II Type II is characterised by a low calcium

and high phosphate levels Therefore tissues are resistant to

parathyroid hormone However, type II is not characterised by

any skeletal changes or the phenotypic appearance of Type 1a

All different physiologies are due to differences in the imprinting defect.

Pseudopseudohypoparathyroidism Phenotypic appearance mimicking those

of pseudoparathyroidism type 1a No lack of parathyroid hormone, no

peripheral resistance to PTH – biochemically normal

Also caused by a defect in the GNAS1 First described by Fuller Albright in 1952

http://www.toptenz.net/top-10-longest-words-in-the-english-language.php