Pseudohypoparathyroidism type 1a presenting as congenital hypothyroidism

Weisman, Yosef; Golander, Avraham; Spirer, Z; Farfel, Zvi

doi:10.1016/s0022-3476(85)80521-7

Cited by 51 publications

(25 citation statements)

References 10 publications

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“…In 3 of our patients, congenital hypothyroidism was the presenting sign of PHP, as described also by Weisman et al [24] and Levine et al [25]. In patients with PHP, the TSH levels are typically elevatedat birth [24, 25,] but may normalize thereafter for a few months before increasing again.…”

Section: Discussionsupporting

confidence: 69%

“…In patients with PHP, the TSH levels are typically elevatedat birth [24, 25,] but may normalize thereafter for a few months before increasing again. The resistance is generally mild, as the elevation in TSH is only minimal,and thyroid hormone levels are normal or slightly low.Goiter is usually absent, consistent with a defect in TSH signaling.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical Heterogeneity of Pseudohypoparathyroidism: From Hyper- to Hypocalcemia

Shalitin

Davidovits²,

Lazar³

et al. 2008

Horm Res Paediatr

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Pseudohypoparathyroidism (PHP) is a rare inherited syndrome characterized by parathyroid hormone (PTH) resistance and is frequently associated with Albright’s hereditary osteodystrophy and resistance to other cAMP-mediated hormones. The usual neonatal presentation is mild primary hypothyroidism secondary to resistance to thyroid-stimulating hormone; hypocalcemia usually develops after age 3–5 years. This work describes the diversity in the clinical expression and course of PHP, with emphasis on calcium levels by age and treatment, in 8 children under long-term follow-up at our pediatric tertiary center. The calcium levels at presentation ranged from transient neonatal hypocalcemia to infantile hypercalcemia to childhood/adolescence hypocalcemia. Interestingly, relative hypocalciuria at diagnosis and during therapy, in the presence of renal PTH resistance, was the rule. These findings indicate that transient neonatal hypocalcemia associated with other clinical features or a family history of PHP may be a flag for clinicians to screen for PTH resistance later in life. In addition, PTH resistance may be missed by surveying calcium levels only; thus the PTH levels have to be checked as well. In addition, the recommendation for patients with hypoparathyroidism that strict low-normal calcium levels be maintained during therapy in order to prevent hypercalciuria is probably not applicable in PHP.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Clinical Heterogeneity of Pseudohypoparathyroidism: From Hyper- to Hypocalcemia

Shalitin

Davidovits²,

Lazar³

et al. 2008

Horm Res Paediatr

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“…The TSH concentration is typically elevated at birth in all newborns with PHP Ia (17)(18)(19) and may subsequently normalize for 9-20 months before increasing again. In PHP Ia patients, this could indicate that, like resistance to PTH (9), resistance to TSH progresses during the first 2 years of life.…”

Section: Discussionmentioning

confidence: 99%

Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH

Balavoine¹,

Ladsous²,

Vélayoudom³

et al. 2008

European Journal of Endocrinology

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Objective: Hypothyroidism is a manifestation of multi-hormonal resistance in pseudohypoparathyroidism type Ia (PHP Ia). The objective of the study was to determine the mechanisms of hypothyroidism in PHP Ia. Design: A prospective study. Patients: Ten patients with PHP Ia. Measurements: The serum concentrations of TSH, free triiodothyronine (FT 3 ), free thyroxine (FT 4 ), and prolactin (PRL) were measured at baseline and after stimulation with TRH (200 mg i.v). Results: The median basal serum TSH concentration was 4.92 mU/l. Basal serum TSH concentration was slightly elevated in eight patients (4.22-7.0 mU/l; normal range, 0.4-3.6 mU/l), normal in one patient (2.5 mU/l), and high in one patient (13.1 mU/l). After the TRH test, TSH concentrations increased to 13.4-36.0 mU/l (normal range, 4.0-20.0 mU/l). The absolute values after the test were normal in three patients and high in seven patients. However, TSH responses relative to the baseline value (stimulated/basal TSH and expressed as a fold increase), which reflect the relative increases after TRH stimulation, were low in seven patients (2.3-to 4.3-fold TSH) and normal in three patients. Basal FT 4 concentration was normal in seven patients and low in three patients (range, 8.4-20.0 pmol/l; mean, 14.1G4.3 pmol/l; normal range, 10.5-23.0 pmol/l). Basal FT 3 concentration was normal in nine patients and low in one patient (range, 0.9-5.0 pmol/l; mean, 3.8G1.1 pmol/l; normal range, 3.3-6.1 pmol/l). FT 4 and FT 3 were not significantly increased after the TRH test. PRL concentration was normal at baseline and increased from 7 to 96 ng/ml after TRH. Conclusion: Our results support the hypothesis that patients with PHP Ia have impaired sensitivity to both TSH and TRH.

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“…However, a few reports describe an early onset of some symptoms characteristic of PHP-Ia at later juvenile or adult stages (see also below; Levine et al 1985, Weisman et al 1985, Yokoro et al 1990, Scott & Hung 1995, Riepe et al 2005, Gelfand et al 2006. From these studies a pattern seems to emerge in which abnormal thyroid function and resistance to thyroid-stimulating hormone (TSH), due to deficient receptor signalling via Ga s , are among the first symptoms detectable: typically, TSH levels are elevated in PHP-Ia at birth (Levine et al 1985, Weisman et al 1985, Yokoro et al 1990. The s.c. ossifications can also develop from the first few months onwards, while resistance to PTH, hypocalcaemia and hyperphosphataemia are usually detected only at later stages of infancy or juvenile age (Eddy et al 2000, Riepe et al 2005, Gelfand et al 2006.…”

Section: Post-natal Physiological Functionsmentioning

confidence: 99%

Physiological functions of the imprinted Gnas locus and its protein variants Gαs and XLαs in human and mouse

Plagge

Kelsey

Germain‐Lee

2007

Journal of Endocrinology

104

137

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The stimulatory a-subunit of trimeric G-proteins Ga s , which upon ligand binding to seven-transmembrane receptors activates adenylyl cyclases to produce the second messenger cAMP, constitutes one of the archetypal signal transduction molecules that have been studied in much detail. Over the past few years, however, genetic as well as biochemical approaches have led to a range of novel insights into the Ga s encoding guanine nucleotide binding protein, a-stimulating (Gnas) locus, its alternative protein products and its regulation by genomic imprinting, which leads to monoallelic, parental origin-dependent expression of the various transcripts. Here, we summarise the major characteristics of this complex gene locus and describe the physiological roles of Ga s and its 'extra large' variant XLa s at post-natal and adult stages as defined by genetic mutations. Opposite and potentially antagonistic functions of the two proteins in the regulation of energy homeostasis and metabolism have been identified in Gnasand Gnasxl (XLa s )-deficient mice, which are characterised by obesity and leanness respectively. A comparison of findings in mice with symptoms of the corresponding human genetic disease 'Albright's hereditary osteodystrophy'/'pseudohypoparathyroidism' indicates highly conserved functions as well as unresolved phenotypic differences.

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Pseudohypoparathyroidism type 1a presenting as congenital hypothyroidism

Cited by 51 publications

References 10 publications

Clinical Heterogeneity of Pseudohypoparathyroidism: From Hyper- to Hypocalcemia

Clinical Heterogeneity of Pseudohypoparathyroidism: From Hyper- to Hypocalcemia

Hypothyroidism in patients with pseudohypoparathyroidism type Ia: clinical evidence of resistance to TSH and TRH

Physiological functions of the imprinted Gnas locus and its protein variants Gαs and XLαs in human and mouse

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