Excessive Thyrotropin Response to Thyrotropin-releasing Hormone in Pseudohypoparathyroidism

Abstract

ExtractIn 8 of 10 patients with pseudohypoparathyroidism, confirmed by increased immunoreactive plasma parathyroid hormone concentrations and/or defective urinary excretion of adenosine 3',5'-monophosphate (CAMP) after parathyroid extract infusion, excessive plasma thyrotropin (thyroid-stimulating hormone) (TSH) response to thyrotropin-releasing hormone (TRH) injection was found. On the other hand, in all seven cases with idiopathic true hypoparathyroidism the TSH response was normal. In two of three patients with pseudopse~dohypoparathyroidisrn, with normal or slightly low plasma calcium, normal or slightly high immunoreactive plasma parathyroid hormone concentration, and intermediate response of cAMP to parathyroid extract, the TSH response to TRH was increased. The results indicate that moderate primary hypothyroidism is frequently present in pseudohypoparathyroidism. Thyroid dysfunction may only be detectable with the use of TSH stimulation by TRH, since clinical signs and other studies of thyroid function did not definitely suggest hypothyroidism in our patients. The rise of TSH is suppressible by thyroxine treatment, but is not influenced by vitamin D treatment. The TSH response to TRH is significantly correlated with the decrease of tubular reabsorption of phosphate after parathyroid extract infusion in with pseudo-and pseudopseudohypoparathyroidism. Speculation TSH stimulation by TRH may be a useful test for the further delineation of biochemical variants of pseudohypoparath yroidism.The occasional association of hypothyroidism with pseudohypoparathyroidism had been suspected for several years (5, 22), but it was only proven in 1960 in a chiId described by Cohen and Donne11 (5). Hypothyroidism was attributed to TSH deficiency, because the ' I uptake by the thyroid gland was increased markedly after TSH administration. Subsequent reports confirmed this finding in additional patients (24,25,27). Recently, however, a mother and her 11-year-oId daughter, who both suffered from pseudohypoparathyroidism, were found to have increased plasma immunoreactive TSH concentrations, which suggested a primary thyroid disorder rather than TSH deficiency (19). In the mother an excessive TSH response to TRH infusion was demonstrated. A similar observation in a child (1 7) prompted the present study of TSH stimulation by TRH in children and adults with pseudohypoparathyroidism. For comparison, TRH tests were also performed in patients with pseudopseudohypoparathyroidism and idiopathic true hypoparathyroidism.

The Pseudohypoparathyroidism Type 1b Locus Is Linked to a Region Including GNAS1 at 20q13.3

“…Two subjects (KII‐3, KII‐5) were obligate carriers and had normal serum levels of calcium, phosphorous, and PTH, as well as normal nephrogenous cAMP responses to infusion of PTH. ( 1–34 ) One affected child (KIV‐2) had normal serum calcium levels and an elevated intact PTH level. This subject was classified as affected with later confirmation of the diagnosis by showing absence of methylation of exon 1A (data not shown).…”

“…In the PHP1a variant of PHP, accessible tissues have demonstrated a 50% reduction in expression and activity of the α chain of G s (G s α) ( 2 , 3 ) owing to heterozygous mutations in the GNAS1 gene located at 20 q13.3. ( 4 ) Patients with PHP 1a are unresponsive to PTH and to several additional hormones whose receptors are coupled to G s ( 5–7 ) and manifest a distinct constellation of developmental and somatic defects, collectively termed Albright hereditary osteodystrophy (AHO). ( 8 ) Many PHP 1a kindreds also contain individuals who have the GNAS1 defect and AHO but also have normal hormone responsiveness, a condition termed pseudo‐pseudohypoparathyroidism (PPHP).…”

Gsα Mutations and Imprinting Defects in Human Disease

“…Almost all PHPIA patients also present with thyrotropin (TSH) resistance,172,173 typically from the time of birth 157,174‐176. The resistance is generally mild with minimally elevated TSH levels and normal or slightly low thyroid hormone levels.…”

Pseudohypoparathyroidism: Its Phenotypic Variability and Associated Disorders in a Large Family

“…Abnormalities of thyroid function are the most common hormonal defect associated with pseudohypoparathyroidism [11,13,36,39,40]. Levine etal.…”