Pseudohypoparathyroidism

Classification according to ICD-10
E20.1	Pseudohypoparathyroidism
ICD-10 online (WHO version 2019)

The Pseudohypoparathyroidism is a rare disease, when symptoms secondary hypothyroidism appear, although the Parathyroid enough parathyroid hormone pours into the blood. The parathyroid hormone does not work because there are phases or permanent disorders of the G-protein-coupled receptor of the parathyroid hormone or the intracellular signal cascade with corresponding organ resistance to parathyroid hormone. The intracellular cAMP production is reduced.

Pseudohypoparathreoidism can occur on its own, but it can also be part of hereditary Albright osteodystrophy , in which there is short stature , a round face , shortened fingers , obesity , subcutaneous calcifications and varying degrees of mental retardation .

In pseudopseudohypoparathyroidism , on the other hand, there is Albright's osteodystrophy without disturbances in calcium metabolism .

Laboratory chemistry shows, as in the classic hypothyroidism, calcium too low ( hypocalcemia ) with increased phosphate ( hyperphosphataemia ), but with normal or increased parathyroid hormone . Phosphorus in the urine is decreased (but increased in hypoparathyroidism). The urinary cAMP level is decreased in type 1, but increased in type 2 and hypoparathyroidism.

Sometimes typical shortenings of the fourth metacarpal bone ( brachymetacarpy ) and the fourth metatarsal bone ( brachymetatarsia ) are found, especially in type 1a, sometimes also in type 1b.

One consequence of Pseudohypoparathyroidism often with elevated PTH is the osteopenia .

Classification

Depending on the appearance, a distinction is made between four types, for which there are also different causes, whereby the delimitation of type 1c is not clear:

• Type Ia : there is also an Albright osteodystrophy . The kidneys are PTH resistant; H. When parathyroid hormone is administered, the concentrations of cAMP and phosphate in the urine do not rise as normally. In addition, there is often resistance to other hormones, especially thyrotropin . The activity of the alpha subunit of the calcium-sensitive G-protein receptor is reduced because the gene GNAS coding for this subunit has a heterozygous loss-of-function mutation , as is typical for Albright osteodystrophy. This affects exons 1-3 of the GNAS gene, which is located in a complex section on chromosome 20 . While splicing alternatives are normally prevented by DNA methylation of the alternative promoters on the maternal or paternal allele , they can now be activated and used as transcript alternatives and the like. a. can be expressed with exon 2-13.

• Type Ib : as with type 1a there is renal PTH resistance, also resistance to other hormones, v. a. Thyrotropin are possible. However, there is no Albright osteodystrophy. The genetic cause is unknown, but there is abnormal methylation of the GNAS gene, which encodes the alpha subunit of the parathyroid hormone's G protein-coupled receptor . This leads to a failure of the expression of the maternal allele.
  Type 1b usually occurs sporadically. A rare variant of type 1b is the paternal uniparental disomy of chromosome 20 , in which only two alleles of the father are present instead of one maternal and one paternal allele.
  Rare familial forms of type 1b can be caused by maternal deletions in the GNAS gene or, more often, in the centromeric STX16 gene for syntaxin 16 .
  Since essentially the maternal GNAS allele is expressed in the proximal tubule of the kidney and the paternal allele hardly contributes to GNAS expression there, loss of the maternal allele explains the PTH resistance in the kidney, as well as in the thyroid gland with thyrotropin resistance and in the pituitary gland.
• Type Ic : is identical to type 1a, except that receptor-independent cAMP production is maintained in vitro . There is a defect in the catalytic unit of the PTH receptor.
• Type II : there are probably several subtypes, there is no Albright osteodystrophy. In contrast to type 1, cAMP production can be stimulated normally. While the phosphorus level in the urine does not rise sufficiently during parathyroid hormone infusion, the cAMP level increases normally. The PTH receptor is intact, the cause is unknown, the disorder is in the area of ​​cAMP-mediated cell stimulation.

therapy

If there is significant hypocalcemia , calcium must be administered intravenously, e.g. B. as calcium gluconate , and later be permanently orally substituted.

Since the phosphorus level is also high ( hyperphosphataemia ), there is a risk that calcium and phosphorus will precipitate and form acute or subacute calcifications in blood vessels, the brain and other soft tissues. This danger exists especially when the product of calcium and phosphorus levels is above 55 mg ² / dl ² . A phosphate binder such as Sevelamer may therefore have to be used.

To improve the enteral absorption of calcium, activated vitamin D must also be given, such as calcitriol , which also reduces PTH secretion and thus diminishes the osteopenic effects.

swell

• Gerd Herold : Internal Medicine 2007

1. ^ Hereditary Albright osteodystrophy The online encyclopedia of dermatology, venereology, allergology and environmental medicine, Springer-Verlag GmbH, Heidelberg, accessed on May 20, 2016
2. ↑ Ryan W. Carroll, Michelle L. Katz, Elahna Paul, Harald Jüppner: Case 17-2017 - A 14-Year-Old Boy with Acute Fear of Choking while Swallowing , New England Journal of Medicine 2017, Issue 376 of June 8th 2017, pages 2266-2275; DOI: 10.1056 / NEJMcpc1616019 (case description of a 14-year-old boy with type 1b)
3. ^ Markus J. Seibel, Hilmar Stracke: Metabolic Osteopathies Schattauer-Verlag Stuttgart 1997, page 216, ISBN 3-7945-1635-4

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