Congenital central hypothyroidism due to a homozygous mutation in the thyrotropin beta-subunit gene follows an autosomal recessive inheritance.

A 5-month-old infant of nonconsanguineous parents had severe hypothyroidism. Undetectable serum levels of T3 and T4 in combination with an undetectable baseline TSH level led to the diagnosis of central hypothyroidism. Administration of TRH failed to increase serum TSH, but not PRL, confirming isolated TSH deficiency. Measurement of the TSH in serum with three different immunoassays that recognize different epitopes of the TSH molecule failed to detect TSH, suggesting an aberrant or absent TSH. Direct sequencing of the entire coding region of the human TSH beta-subunit gene revealed a homozygous single base pair deletion in codon 105, resulting in a frame shift with a premature stop at codon 114. The truncated TSH beta peptide lacks the terminal five amino acids. Furthermore, the cysteine in codon 105 that is believed to be important for the interaction of the TSH beta-subunit with the alpha-subunit, is replaced with a valine (C105V), supporting the theory of a conformational change in the TSH molecule. Genotyping confirmed that the proposita was homozygous for this mutation, whereas her unaffected parents, the paternal grand-mother, and the maternal grandfather were heterozygous. Thus, isolated TSH deficiency follows an autosomal recessive mode of inheritance in this kindred.

Diagnosis and management of juvenile hyperthyroidism in Germany: a retrospective multicenter study.

This retrospective multicenter study was designed to survey the management of childhood and adolescent hyperthyroidism in six pediatric endocrinological units in Germany. Fifty-six patients aged between 1.1 and 17.0 yr (median 10.5 yr) were enrolled. Data were collected retrospectively from the patients' records by a trained pediatric endocrinologist using standardized questionnaires. After the diagnosis of hyperthyroidism was established on the basis of clinical and biological findings, treatment with antithyroid drugs (carbimazole, methimazole, thiamazole, propylthiouracil) was started in all patients. In 55/56 of the patients treated with antithyroid drugs, euthyroidism was achieved (98%). However, 26 patients (47%) were still hyperthyroid after discontinuation of the medication. Eight children with continued hyperthyroidism ultimately underwent subtotal thyroidectomy 13-136 (median 28) months after the initial diagnosis. Management principles of the participating centers were heterogeneous. As a consequence, prospective multicenter studies are urgently needed to establish clear standards for the diagnosis and therapy of childhood hyperthyroidism.

[Congenital hypothyroidism: causes for delayed initiation of treatment]. / Angeborene Hypothyreose: Ursachen eines verzögerten Behandlungsbeginns.

The aim of neonatal screening programs for congenital hypothyroidism is to ensure early treatment in order to prevent brain dysfunction. There are several reasons why infants are missed in the screening program. We report on three patients with congenital hypothyroidism, who had a pathological screening result and initiation of therapy was delayed. The first patient had an increased TSH level, but she was missed because of mistakes in the confirmatory serum test. During the follow-up the patient showed typical symptoms of hypothyroidism and got a thyroxine supplementation not before the age of three years. The second patient did not get a therapy before the age of six months because of the noncompliance of the parents and physicians. The third patient had a central hypothyroidism. The neonatal screening-program revealed no measurable TSH activity. Although the child had clinical signs of a severe hypothyroidism diagnosis was not made before the age of 5.5 months. Although different reasons are known for screening errors, all these 3 patients were missed because of failures in the follow-up of a pathological screening result, indicating a poor quality in the follow-up procedure.

[Autoimmune thyroiditis in children and adolescents: clinical and laboratory findings in 34 patients]. / Die Autoimmunthyreoiditis bei Kindern und Jugendlichen: Klinische und biochemische Befunde bei 34 Patienten.

Autoimmune thyroiditis (AT) is the most common cause of nonendemic thyromegaly and acquired hypothyroidism in childhood and adolescence. Outgoing from an increasing number of newly diagnosed patients during the last years we performed a retrospective analysis including 34 patients treated between 1989 and 1998. Clinical data, laboratory and sonographical findings are described. Cases were ascertained by palpable thyroid enlargement or clinical signs of thyroid dysfunction and positive autoantibodies against thyroid tissue. Frequency of AT diagnosis has threefold increased since 1995 in our department. Age at diagnosis was 5.4 to 16.3 years (median 11.3). Palpable thyromegaly was present in 29 (85%) of our patients. Three patients had myxedema without goiter. Symptoms had been present for a period between 6 weeks and 7.5 years: median in all patients 6 months, median in hypothyroid patients 9 months. At time of diagnosis 15 patients suffered from hypothyroidism, 3 from hyperthyroidism and 7 patients showed normal levels of thyroid hormones. In 9 patients we found an isolated elevation of thyrotropin. 12 patients were prepubertal (Tanner I), 15 patients were pubertal (Tanner II-IV). 5 patients showed a dissociation of pubertal maturation. Ultrasound of thyroid gland showed an inhomogeneous and hypoechoic pattern in 32 patients. 30 patients were treated with thyroxine. Patients with persistent hyperthyroidism were treated with carbimazol. During the follow-up period enlargement of the thyroid gland decreased in one third of the patients. Thyromegaly caused by autoimmune thyroiditis gets an increasing importance. The high degree of obviously hypothyroid patients at the time of diagnosis reflects a delay of diagnosis. Early recognition and treatment of the disease should be achieved for a preventive care of hypothyroidism.

[Interstitial lung diseases with pulmonary hypertension associated with epidermolysis bullosa in an infant]. / Interstitielle Lungenerkrankung mit pulmonaler Hypertension assoziiert mit Epidermolysis bullosa bei einem Säugling.

Interstitial lung diseases, with or without pulmonary hypertension and epidermolysis bullosa are rare in infancy. Pathogenetic correlations between these disease are not known and their coincidence has not been reported, yet. We report on a seven weeks old boy of consanguine parents with typical skin efflorescences of epidermolysis bullosa, tachydyspnoea and cyanosis. Echocardiography and cardiac catheterisation revealed pulmonary hypertension, which persisted under therapy with oxygen and nifedipin. Lung biopsy showed interstitial and peribronchiolar increased lymphocytes and lymphfollicels, a mild intraalveolar desquamation and a media hypertrophy of the arteries. A combined therapy of prednisone and nifedipine normalised the pulmonary hypertension and the oxygen saturation. The activity of the epidermolysis bullosa showed no correlation with the interstitial lung disease or with the therapy. A connection between both diseases is discussed.

Liquorice, growth retardation and Addison's disease.

An 11-year-old boy had hypoparathyroidism and Addison's disease. During treatment with calcitriol, calcium, hydrocortisone and 9-alpha-fluorocortisol, he developed an apparent mineralocorticoid excess and growth retardation. Pseudohyperaldosteronism even persisted after treatment with 9-alpha-fluorocortisol was stopped and hydrocortisone was reduced to 6 mg/m(2). The boy reported an excessive daily intake of 300-400 g liquorice corresponding to 600-800 mg glycyrrhizic acid because of salt craving. After complete withdrawal of liquorice all symptoms of hypermineralocorticoidism diminished and growth velocity increased. We hypothesise that inhibition of 11beta-hydroxysteroid dehydrogenase by liquorice caused hypermineralocorticoidism and growth retardation via increased levels of free cortisol in this patient. We conclude that self-medication with liquorice in children with Addison's disease should be considered during treatment.

[Psychosocially stunted growth masked as growth hormone deficiency]. / Psychosozialer Kleinwuchs maskiert als Wachstumshormonmangel.

Short stature is a common reason for presenting a child to the pediatrician. Emotional deprivation may cause short stature and may simulate growth hormone deficiency. Diagnosis of emotional deprivation as the cause of growth retardation is difficult and misdiagnosed frequently despite of suspicious clinical signs. We report on 2 patients with growth retardation because of emotional deprivation. At the age of 5 years both children had a severe growth hormone deficiency. They received therapy with growth hormone and showed an increase of growth velocity to > or = 8 cm in the first year of treatment. But in the third year of treatment both patients showed a diminished response to the growth hormone therapy. During the period of observation the features of emotional deprivation became obvious through the extreme behavioural abnormalities. Both children showed disturbances in their social behaviour, and striking disorders concerning eating and digestion. The families of these children had severe social problems; alcoholism, low income and rejection of the child were risk factors. Removal from the current environment led to a characteristic increase of the growth velocity. Growth hormone deficiency was spontaneously reversible, so that treatment with growth hormone was terminated. The social environment and the psychical prosperity are essential growth factors in childhood and adolescence. The common features and risk factors of emotional deprivation are described. Spontaneous catch-up growth after removal from the current environment distinguishes this form of short stature from the other organic growth disorders.

Induction of early puberty in a boy after treatment with oxandrolone?

We report on a 9-year-old boy with early puberty who had been treated with oxandrolone because of constitutional delay of growth. Treatment was started at the age of 6.25 years. During the treatment with oxandrolone over 22 months, the height velocity increased above the 97th percentile, and bone age developed twice as fast as chronological age. After discontinuing the medication, the growth velocity did not decrease, and the bone age still accelerated. When he was 9.1 years old, testicular volume had increased to 12 ml, pubic hair stage had progressed and he developed a mild facial acne. We hypothesize that oxandrolone could have induced an early onset of puberty in this boy. We conclude that treatment with oxandrolone in young children should be considered carefully and be used for short periods only. Potential side effects might include the rapid acceleration of puberty and skeletal maturation.

[Steroids for prophylaxis of nephropathy in Schnlein Henoch purpura? Follow-up of 171 patients]. / Steroide zur Prophylaxe der Purpura Schönlein Henoch Nephropathie? Verlaufsbeobachtung bei 171 Patienten.

UNLABELLED: The necessity of the controversially discussed general steroid prophylaxis in Henoch-Schönlein Purpura (HSP) was analysed based on frequency, risk factors and prognosis of renal involvement. Case histories and follow up of at least 1.5 years were evaluated in all 171 patients (median age 6 years) in our institution suffering from HSP between 1.1.1987 and 30.6.1997. HSP was frequently manifest with an involvement of joints (64%) and gastrointestinal tract (58%). Renal involvement occurred in only 29% of the children. Excepted one girl (age 12 year), all children with renal disease completely recovered. Renal involvement was significantly rarer in young children (16%) and after one week therapy with prednisone (7%). In young children, renal involvement always followed abdominal pain. CONCLUSION: In our collective, a general preventing of renal disease in HSP was unnecessary. Especially in young children, the most common manifestation age, renal involvement rarely occurred and had always a good prognosis.