Adult-onset reversible idiopathic hypogonadotropic hypogonadism in male adult carrying a WDR11 missense mutation.

The patient developed adult-onset IHH after having his first child, presenting initially with gynecomastia.

• The patient was a man in his 20s who had already fathered one child prior to diagnosis.
• Initial presentation was gynecomastia, which led to the subsequent diagnosis of IHH.
• This represents an unusual adult-onset presentation, as IHH occurs mostly in childhood or adolescence and very rarely in adulthood.
• The case is notable because adult-onset IHH is characterized by delayed onset of secondary sexual characteristics in typical congenital cases, but this patient had prior normal reproductive function.

The patient carried a heterozygous missense variant in WDR11 (c.2390G>A; p.Arg797His) that may have contributed to adult-onset IHH and its reversal.

• The variant identified was a heterozygous missense mutation: c.2390G>A; p.Arg797His in the WDR11 gene.
• Many genetic abnormalities have been reported in congenital IHH cases, but genetic findings are rarely reported in adult-onset IHH cases.
• The authors suggest this WDR11 variant 'may play a role in adult-onset IHH reversal.'
• WDR11 mutations have been previously associated with IHH, and this case adds to understanding of the genetic component of the condition.

The patient's IHH was reversible; he responded to gonadotropin-releasing hormone replacement therapy, fathered two additional children, and sustained improvement after treatment discontinuation.

• The patient was treated with gonadotropin-releasing hormone replacement therapy.
• During treatment, he fathered two more children (for a total of three children).
• Treatment was discontinued after 4 years.
• Improvement was sustained after treatment discontinuation, consistent with the reversibility of IHH.
• The authors note that 'IHH requires lifelong hormone replacement therapy; however, a few reports suggest the reversibility of this condition,' placing this case among rare reversible IHH cases.

Accumulation of adult-onset reversible IHH cases with identified genetic variants may contribute to understanding of IHH pathogenesis.

• The authors state that 'accumulation of such cases can contribute to our understanding of the pathogenesis and genetic component of IHH.'
• Genetic abnormalities have been rarely reported specifically in adult-onset IHH cases.
• The identification of a WDR11 missense variant in this reversible adult-onset case highlights the potential genetic underpinnings of atypical IHH presentations.