Longevity of the hypopituitary patients from the island Krk: a follow-up study.

Patients with dwarfism on the Krk island in the Adriatic Sea have been known since 1864. Since then 25 related dwarfs (15 males and 10 females) originating from the villages Bascanska Draga and Jurandvor have been recorded. The last patient was born in 1996 and was diagnosed in 2004. In 1988 we were able to prove that the etiology of the hereditary multiple pituitary deficiencies (MPHD) causing the dwarfism is due to a PROP-1 gene mutation, a pituitary transcription factor. During visits in 1988, 1990 and 2007 data on the life span of these patients not treated by growth and sex hormone were collected. We found data for 9 patients (5 males and 4 females). One female died in an accident at age 61; 6 patients (3 males and 3 females) died between ages 68 and 91 due to cardiovascular disease. Two males died at ages 77 and 83, cause unknown. It is concluded that despite the long lasting GH and sex hormone deficiencies and irregular thyroid hormone ingestion, patients with congenital MPHD due to Prop-1 gene defects can live a long life.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in croatia between 1995 and 2006.

AIMS: To evaluate the incidence, gender, symptoms and age at diagnosis among patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency in Croatia. METHODS: Data were collected retrospectively for all classical CAH patients born or electively aborted following prenatal diagnosis between 01.01.1995 and 31.12.2006 and were compared with the data of the previously conducted study evaluating CAH patients discovered between 1964 and 1984. RESULTS: During a 12-year period, 34 classical CAH patients were born. There were 20 salt-wasting (SW) (12 females/8 males) and 14 simple virilizing (SV) patients (7 females/7 males). If 3 female fetuses, electively aborted, were added, that would be a total of 37 CAH patients. With 532,942 live births and 34 CAH patients born over this period, incidence of classical CAH was estimated to 1:15,574 or 1:14,403 if 3 electively aborted fetuses were included. The lower incidence of SW boys compared to SW girls (8:12) and similar number of SW and SV boys (8:7) indicate that substantial proportion of SW boys die unrecognized. Owing to better health care, diagnosis was established significantly earlier in SW and SV girls compared to the period of 1964-1984 (p < 0.003). During 1995-2006, none of the patients died following the diagnosis of CAH, and there was no erroneous sex assignment. CONCLUSION: Despite of improvement in health care, diagnosis of CAH in Croatia is still delayed and some of the patients go unrecognized or die. Therefore, we think that the results of our study support the need for the introduction of newborn screening.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency in Croatia between 1995 and 2006.

AIMS: To evaluate the incidence, gender, symptoms and age at diagnosis of patients with classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency in Croatia. METHODS: Data were collected retrospectively for all classical CAH patients born or electively aborted following prenatal diagnosis between January 1, 1995 and December 31, 2006 and were compared with the data of a previously conducted study evaluating CAH patients discovered between 1964 and 1984. RESULTS: During a 12-year period 34 classical CAH patients were born. There were 20 salt-wasting (SW; 12 female/8 male) and 14 simple-virilizing (SV; 7 female/7 male) patients. If 3 female, electively aborted fetuses were added, there would be a total of 37 CAH patients. With 532,942 live births and 34 CAH patients born over this period, the incidence of classical CAH was estimated at 1:15,574 or 1:14,403 if the 3 electively aborted fetuses were included. The lower incidence of SW boys compared to SW girls (8:12) and similar number of SW and SV boys (8:7) indicate that a substantial proportion of SW boys die unrecognized. Owing to better healthcare, the diagnosis was established significantly earlier in SW and SV girls compared to the period of 1964-1984 (p < 0.003). During 1995-2006, none of the patients died following the diagnosis of CAH and there was no erroneous sex assignment. CONCLUSION: Despite improvements in healthcare, the diagnosis of CAH in Croatia is still delayed and some of the patients go unrecognized or die. Therefore, the results of our study support the need to introduce newborn screening.

Epidemiology and clinical characteristics of thyroid dysfunction in children and adolescents with type 1 diabetes.

The aim of the study was to evaluate the natural course and potential risk factors of autoimmune thyroiditis (AIT) and thyroid dysfunction, and their influences on growth and glycemic control in children and adolescents with type 1 diabetes mellitus (T1D). The study comprised 148 subjects (age range 1-21 years; males 51%) with T1D. During the interval of 12 years serum levels of thyroid peroxidase (anti-TPO) and thyroglobulin (anti-TG) autoantibodies, thyroid-stimulating hormone (TSH) and tyroksine (T4), were screened annually. Height, weight, body mass index (BMI), glycosylated hemoglobin (HbA1c), insulin dose and the number of severe hypoglycemic episodes, were recorded every 3 months. The mean follow-up was 7 +/- 4.1 years. Prevalence of AIT in subjects with T1D was 15.5%. It was significantly higher in girls (21.9% vs. 9.3%; p = 0.03). The mean age at AIT onset was 11.5 +/- 5.2 years. The mean interval between negative and positive AIT screening was 2.5 +/- 2.3 years. Cumulative incidence of AIT after 6 years of T1D duration was significantly higher in girls (30% vs. 15%; p = 0.03). Prevalence of hypothyroidism was 8.1% with no significant differences in sex distribution. Prevalence of hypothyroidism among subjects with elevated serum thyroid antibodies was 52.2% with significant male preponderance (85.7% vs. 37.5%; p = 0.005). There were no subjects who developed hypothyroidism in absence of thyroid antibodies. Cumulative incidence of hypothyroidism after 3 years from the moment of thyroid antibodies appearance was 55% with significant male preponderance (85% vs. 40%; p = 0.005). The mean interval between T1D onset and hypothyroidism development was 3.3 +/- 2.5 years, and between thyroid antibodies appearance and hypothyreoidism development was 1.7 +/- 1.2 years. The mean age at hypothyroidism onset was 12.7 +/- 5.3 years. There were no differences in growth and metabolic control between patients with and without AIT. The results of the present study confirmed frequent occurrence of AIT and thyroid dysfunction in subjects with T1D. The number of newly diagnosed subjects with AIT reached the peak at the age of puberty. Girls were significantly more predisposed to AIT at any age while amongst subjects with elevated thyroid antibodies boys developed hypothyroidism more frequently. Annual screening of thyroid antibodies in all patients with T1D is recommended, while serum TSH level should be measured in patients with detected thyroid antibodies.

Steroid diabetes in children with Crohn disease.

Glucocorticoids may be useful as short-term palliative therapy for acute exacerbations of Crohn disease. When glucocorticoids are used for longer than brief periods, even in moderate dosages, they can produce a variety of adverse effects, including steroid diabetes. Two boys were treated with methylprednisolone due to acute exacerbations of Crohn disease. After five and six weeks of continuous oral administration of methylprednisolone, the boys developed steroid diabetes. Diabetic symptoms dominated the clinical presentation but there was no tendency towards diabetic ketoacidosis. Reduction of methylprednisolone dosage rather than insulin therapy resulted in better control of glycemia. Frequent blood glucose monitoring is recommended in children on prolonged therapy with glucocorticoids. Steroid diabetes experienced by the reported cases may be a marker for the onset of diabetes in their adulthood.