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.

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.