Hypogonadotrophic hypogonadism and primary amenorrhoea associated with increased melatonin secretion from a cystic...

A 17-year-old girl presented with primary amenorrhoea and failure to develop secondary sexual characteristics, although her height was above the 90th centile. Endocrine investigations revealed hypogonadotrophic hypogonadism (basal LH and FSH levels < 0.5 U/l; FSH rose to 2.0 U/l and LH to 1.0 U/l after GnRH). ACTH, GH, TSH and PRL secretion were normal. A magnetic resonance scan revealed no abnormality in the pituitary, pituitary stalk or hypothalamus but demonstrated a partly cystic enhancing lesion in the pineal region. Melatonin production (assessed as urinary 6-sulphatoxymelatonin: aMT6s) at baseline was markedly increased: 459-530 ng/kg/24 h compared with aged-matched controls: 136 +/- 69 (P = 0.01). However, melatonin production retained a largely normal rhythm with increased production during the night. Treatment with ethinyloestradiol 100 micrograms daily had no apparent effect on the production of melatonin. Treatment with atenolol, 100 mg daily at 1600 h, was associated with suppression of nocturnal melatonin secretion but a brisk rebound in the morning and a considerably delayed peak excretion time (10.2 h) compared with controls (3.9 h). It is likely the pineal lesion, which may be hyperplasia or possibly even tumour, was responsible for the increased melatonin secretion. These data support the hypothesis that melatonin may have a causal role in hypogonadotrophic hypogonadism.