Isolated transient neonatal clitoromegaly with hyperandrogenism of unknown etiology.

BACKGROUND: Neonatal clitoromegaly is usually attributed to androgen stimulation secondary to congenital adrenal hyperplasia or in utero androgen exposure. We present a unique case of transient, isolated neonatal clitoromegaly, associated with increased androgen levels of unidentifiable cause, which spontaneously resolved when the androgen levels normalized. This is the first report where, despite an exhaustive workup, the cause of hyperandrogenism remains unknown. CASE: A female infant was delivered at 25 + 5 weeks gestational age. Clitoromegaly was first documented at 3 months of age (18 mm long, |13 mm wide). There was no other evidence of virilization. There was no neonatal history of transfusions or androgen-medication exposure. Initial bloodwork documented extremely high levels of free testosterone (117 pmol/L) and dehydroepiandrosterone sulfate (DHEAS). Further tests ruled out the following diagnoses: 21-hydroxylase deficiency, 11-betahydroxylase deficiency, testicular feminization, presence of ovotesticular tissue, and androgen-secreting tumors. Maternal history ruled out in utero androgen exposure, maternal drug use, hyperandrogenism, or virilization during pregnancy, and antenatal imaging had not detected a maternal ovarian mass or adrenal tumor. The infant's androgen levels spontaneously declined, and by 4 months of age had normalized without therapy (free testosterone 8 pmol/L). At 5 months of age, the clitoral measurements normalized (10mm long, 5mm wide). CONCLUSION: In this case of a premature female infant, hyperandrogenism and clitoromegaly resolved spontaneously. Only 1 other case of hyperandrogenism and clitoromegaly that resolved spontaneously in a preterm infant has been reported. In that case, the clitoromegaly and high testosterone levels were attributed to repeated blood transfusions from an adult male. The etiology of the hyperandrogenism and resultant clitoromegaly in our case is not known.

Virilizing luteinized thecoma of the ovary in a 15-year-old female: a case report.

BACKGROUND: Only 30% of luteinized thecomas are found in women under the age of 30, and they are typically benign. Only 11% of luteinized thecomas show clinical signs of androgen production. We present an unusual case of a 15-year-old female who presented with secondary amenorrhea and virilization and was subsequently diagnosed with a benign luteinized thecoma of the ovary. This is the youngest nonmalignant luteinized thecoma reported to date. CASE: A 15-year-old Sri Lankan female presented with increasing hair growth, a hoarse voice, and secondary amenorrhea. On physical examination, there was marked hirsutism and clitoromegaly. Investigations found an elevated free testosterone level and an enlarged, homogenous left ovary with absent normal ovarian architecture. A laparotomy and unilateral salpingo-oophorectomy was performed. The final diagnosis was a luteinized ovarian thecoma, with no evidence of malignancy. Postoperatively, testosterone levels normalized and menstrual cycles resumed. Although laser treatment helped with her hirsutism, her other virilizing symptoms (deepening of voice, clitoromegaly) did not improve postoperatively. CONCLUSION: This case of a virilizing ovarian luteinized thecoma emphasizes the need for timely evaluation, diagnosis, and treatment of patients presenting with symptoms of excess androgen secretion in order to avoid irreversible unwanted effects. Possible ovarian causes of excess androgen secretion should not be overlooked when considering possible causes of hyperandrogenism and secondary amenorrhea.

Synthesis and biological evaluation of S-adenosyl-1,12-diamino-3-thio-9-azadodecane, a multisubstrate adduct inhibitor of spermine synthase.

As part of a continuing search for specific inhibitors of the enzymes involved in polyamine biosynthesis, we have designed and synthesized a multisubstrate adduct inhibitor, S-adenosyl-1,12-diamino-3-thio-9-azadodecane (AdoDATAD), in which critical portions of the nucleophilic aminopropyl acceptor are covalently linked to critical portions of the electrophilic aminopropyl donor to form a potent and specific inhibitor of spermine synthase. In addition, the corresponding desamino analogue which was designed to lack activity against spermine synthase on the basis of substrate structure-activity data has been synthesized as a control. Preliminary biological results demonstrate that AdoDATAD is a potent and specific inhibitor of mammalian spermine synthase in vitro, while being almost completely devoid of inhibitory activity toward the closely related aminopropyltransferase spermidine synthase. The desamino analogue, as predicted, showed no inhibitory activity against either enzyme. AdoDATAD represents an important addition to the arsenal of specific enzyme inhibitors available for blockade of the polyamine biosynthetic pathway at specific sites.