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Medicine

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Endocrine

Question
2 out of 6
 

One of the mutations in pseudo hyperparathyroidism is in gene for Gs-Alpha. This mutation mostly results in? (AIIMS May 2014)



A Gain of function mutation

B Reduced GTPase activity of Gs-Alpha subunits

C Reduced synthesis of cAMP in response to PTH

D Reduced generation of inositol triphosphate

Ans. C

Reduced synthesis of cAMP in response to PTH.

Causes of hypoparathyroid:

1). Primary (due to gland failure)

a. Idiopathic (Autoimmune) (associated with other autoimmune disorders),

Lab tests of Idiopathic hypoparathyroid - Ca2+, PO43-. (Serum ALP is not raised)

Treatment = alpha calcidiol and calcium supplement.

b. Infantile hypoparathyroidism: It is associated with thymic aplasia (Di George syndrome)

2). Secondary

a. Post-operative : surgery (thyroidectomy).

b. Post radio iodine therapy

c. Hypomagnesemia – (Mg is required for PTH secretion)

3). Pseudohypoparathyroidism (PHP) (Ref. Hari-18th ed.,Pg-3118)

a. It is a group of disorders characterized by hypocalcemia due to renal resistance to PTH.

b. PTH levels are high.

c. Various phenotypic abnormalities may be tissues are associated—classically, short stature, round face, obesity, short fourth metacarpals, ectopic bone formation, and mental retardation. Cataract.

d. Treatment is same as for primary.

4). “Pseudopseudohypoparathyroidism(PPHP)

a. Patients without hypocalcemia but sharing the phenotypic abnormalities (as of pseudo hypoparathyroidism)..

b. These patient have normal serum calcium and high serum PTH.

c. In pseudohypoparathyroidism, defect lies at PTH receptor level. While in pseudo pseudohypoparathyroidism defect lies at gene transcription level beyond the PTH receptors.

Mutations in pseudohypoparathyroidism is in gene for Gs-Alpha mostly results in:(AIPG 2011)

1). In PHP, there is reduced synthesis of cAMP in response to PTH so there is no appropriate increase in the urinary cAMP occurs (AIIMS Nov 2011)

2). In PPHP there is increased synthesis of cAMP in response to PTH so there is increase in the urinary cAMP occurs.

3). Both patterns of inheritance lead to Albright’s hereditary osteodystrophy (AHO), because of haplotype insufficiency—i.e., both copies of Gs alpha must be active in the fetus for normal bone development.

Pseudopseudohypoparathyroidism can be best understood by comparing it to other conditions:

Condition

PTH levels

Calcium

(Pattern of inheritance)

Imprinting

Hypoparathyroidism

Low

Low

Not applicable

Pseudohypoparathyroidism

Increase

Low

Gene defect from mother

Pseudopseudohypoparathyroidism

Increase

Normal

Gene defect from father