Pseudohypoparathyroidism is characterized by peripheral resistance to parathyroid hormone rather than a deficiency, causing hypocalcemia and hyperphosphataemia. There are three main types - 1a, 1b, and 2 - which are all heterozygous genetic conditions involving haploinsufficiency of the GNAS1 gene. Type 1a is associated with short stature, round face, soft tissue calcification, and developmental delays. The molecular defect is in the GNAS1 gene which encodes the Gsa protein involved in several hormone signaling pathways. Types 1b and 2 also involve GNAS1 defects but have different clinical presentations and endocrinological effects.

1. The pseudos
Pseudo from the greek – false
or lying
Samantha Harrison MBBS 3
KCL

2. 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

3. 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

4. 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

6. 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

7. 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.

8. 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.

9. 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
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