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Impaired IGF1-GH axis and new therapeutic options in Alström Syndrome patients: a case series.

Mihai CM, Catrinoiu D, Toringhibel M, Stoicescu RM, Ticuta NP, Anca H - Cases J (2009)

Bottom Line: The patients were hospitalized and the growth hormone stimulatory tests were made, as well as brain MRI.Insulin provocative test revealed a severe GH deficiency in these patients, defined by a peak response to insulin-induced hypoglycemia less than 3 ng/dl and IGF1 concentrations less than - 2SDS.We didn't find multiple pituitary hormone deficiency and we noticed only a severe GH deficiency in all three patients.Future studies are needed to assses if the substitution therapy with Recombinant Growth hormone is cost-effective and without risk in such patients with Alström Syndrome and severe insulin resistance, despite our good results in one patient.

View Article: PubMed Central - HTML - PubMed

Affiliation: "Ovidius" University Constanta, Faculty of Medicine, Constanta County Emergency Hospital, 145 Tomis Blvd, 900591, Constanta, Romania. cristina2603@yahoo.com.

ABSTRACT

Background: Defects of the primary cilium and its anchoring structure, the basal body, cause a number of human genetic disorders, collectively termed ciliopathies: primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration.Alström syndrome is an extremely rare, autosomal recessive genetic disorder characterized by a group of signs and symptoms including infantile onset dilated cardiomyopathy, blindness, hearing impairment/loss, obesity, diabetes, hepatic and renal dysfunction.Because adult growth hormone deficiency and Alström Syndrome share some clinical and metabolic features, we studied the GH-IGF1 axis, using MRI techniques and dynamic tests in 3 unrelated patients with Alström syndrome.

Case presentation: The patients were hospitalized and the growth hormone stimulatory tests were made, as well as brain MRI. Insulin provocative test revealed a severe GH deficiency in these patients, defined by a peak response to insulin-induced hypoglycemia less than 3 ng/dl and IGF1 concentrations less than - 2SDS.We didn't find multiple pituitary hormone deficiency and we noticed only a severe GH deficiency in all three patients. The MRI study of the diencephalic and pituitary region was suggestive for the diagnosis of empty sella in one patient.One patient received Recombinant-GH replacement for one year with very good results, one underwent a gastric sleeve with a satisfactory outcome, one patient died due to the progression of the cardiac myopathy.

Conclusion: Future studies are needed to assses if the substitution therapy with Recombinant Growth hormone is cost-effective and without risk in such patients with Alström Syndrome and severe insulin resistance, despite our good results in one patient. Also, careful clinical and genetic studies can contribute to a better understanding of the evolution after different therapeutical attempt in the complex disorders such as Alström Syndrome.

No MeSH data available.


Related in: MedlinePlus

Patient 1.
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Figure 1: Patient 1.

Mentions: The first patient diagnosed with Alström syndrome in our department was a 20-year-old boy, born from a non-consanguineous parents. During his first year of life were noted increased weight gain and progressive and worsening pathological ocular signs: nystagmus (at 4 months) and photophobia (at 12 months), reduced visual acuity. Sensorineural hearing impairment was noted at 15 years of age and type 2 diabetes mellitus was diagnosed at 16 years of age (Figure 1). From that point, he has been on insulin therapy, in different protocols, with 3 of 4 injections/day. The needed dose of insulin in order to obtain a good glycemic control was more than 200 IU/day. At this point, diabetes mellitus was considered as the result of resistance to the action of insulin. He never developed ketosis or diabetic keto-acidosis (DKA). Also, abnormal liver and kidney function tests were noted, an increased level of triglycerides with normal cholesetrol, with normal intelligence, normal extremities, normal secondary sexual characteristics. Systolic dysfunction of the left ventricle was diagnosed by echocardiography (long parasternal axis showed diffuse hypokinesia with mitral valve failure). Using Tissue Doppler Application, longitudinal velocity shortening and pulmonary hypertension 65–70 mmHg were also found.


Impaired IGF1-GH axis and new therapeutic options in Alström Syndrome patients: a case series.

Mihai CM, Catrinoiu D, Toringhibel M, Stoicescu RM, Ticuta NP, Anca H - Cases J (2009)

Patient 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2648950&req=5

Figure 1: Patient 1.
Mentions: The first patient diagnosed with Alström syndrome in our department was a 20-year-old boy, born from a non-consanguineous parents. During his first year of life were noted increased weight gain and progressive and worsening pathological ocular signs: nystagmus (at 4 months) and photophobia (at 12 months), reduced visual acuity. Sensorineural hearing impairment was noted at 15 years of age and type 2 diabetes mellitus was diagnosed at 16 years of age (Figure 1). From that point, he has been on insulin therapy, in different protocols, with 3 of 4 injections/day. The needed dose of insulin in order to obtain a good glycemic control was more than 200 IU/day. At this point, diabetes mellitus was considered as the result of resistance to the action of insulin. He never developed ketosis or diabetic keto-acidosis (DKA). Also, abnormal liver and kidney function tests were noted, an increased level of triglycerides with normal cholesetrol, with normal intelligence, normal extremities, normal secondary sexual characteristics. Systolic dysfunction of the left ventricle was diagnosed by echocardiography (long parasternal axis showed diffuse hypokinesia with mitral valve failure). Using Tissue Doppler Application, longitudinal velocity shortening and pulmonary hypertension 65–70 mmHg were also found.

Bottom Line: The patients were hospitalized and the growth hormone stimulatory tests were made, as well as brain MRI.Insulin provocative test revealed a severe GH deficiency in these patients, defined by a peak response to insulin-induced hypoglycemia less than 3 ng/dl and IGF1 concentrations less than - 2SDS.We didn't find multiple pituitary hormone deficiency and we noticed only a severe GH deficiency in all three patients.Future studies are needed to assses if the substitution therapy with Recombinant Growth hormone is cost-effective and without risk in such patients with Alström Syndrome and severe insulin resistance, despite our good results in one patient.

View Article: PubMed Central - HTML - PubMed

Affiliation: "Ovidius" University Constanta, Faculty of Medicine, Constanta County Emergency Hospital, 145 Tomis Blvd, 900591, Constanta, Romania. cristina2603@yahoo.com.

ABSTRACT

Background: Defects of the primary cilium and its anchoring structure, the basal body, cause a number of human genetic disorders, collectively termed ciliopathies: primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration.Alström syndrome is an extremely rare, autosomal recessive genetic disorder characterized by a group of signs and symptoms including infantile onset dilated cardiomyopathy, blindness, hearing impairment/loss, obesity, diabetes, hepatic and renal dysfunction.Because adult growth hormone deficiency and Alström Syndrome share some clinical and metabolic features, we studied the GH-IGF1 axis, using MRI techniques and dynamic tests in 3 unrelated patients with Alström syndrome.

Case presentation: The patients were hospitalized and the growth hormone stimulatory tests were made, as well as brain MRI. Insulin provocative test revealed a severe GH deficiency in these patients, defined by a peak response to insulin-induced hypoglycemia less than 3 ng/dl and IGF1 concentrations less than - 2SDS.We didn't find multiple pituitary hormone deficiency and we noticed only a severe GH deficiency in all three patients. The MRI study of the diencephalic and pituitary region was suggestive for the diagnosis of empty sella in one patient.One patient received Recombinant-GH replacement for one year with very good results, one underwent a gastric sleeve with a satisfactory outcome, one patient died due to the progression of the cardiac myopathy.

Conclusion: Future studies are needed to assses if the substitution therapy with Recombinant Growth hormone is cost-effective and without risk in such patients with Alström Syndrome and severe insulin resistance, despite our good results in one patient. Also, careful clinical and genetic studies can contribute to a better understanding of the evolution after different therapeutical attempt in the complex disorders such as Alström Syndrome.

No MeSH data available.


Related in: MedlinePlus