Premature Pubarche, Hyperinsulinemia and Hypothyroxinemia: Novel Manifestations of Congenital Portosystemic Shunts (Abernethy Malformation) in Children

Abstract

Congenital portosystemic shunt (CPSS) is persistence of an anomalous embryological connection of the portal vein with a large vein of the vena cava system. Clinical presentations include neonatal cholestasis, liver tumors, and encephalopathy, but can be variable in timing and symptomatology. We report 2 girls who presented 10 years apart with the same complaint of early pubarche at age 7 years, with inappropriately low DHEAS levels. In addition to hyperandrogenemia (elevated testosterone and androstenedione) and advanced bone age, both had hyperinsulinemia, and hypothyroxinemia. The 2nd case also had symptomatic hypoglycemia. Presentation of CPSS with this combination of findings in prepubertal children has not been reported previously. With further investigations, we proposed novel mechanisms explaining these manifestations. Hyperandrogenemia is caused by decreased hepatic sulfation of DHEA to less active DHEAS due to shunting of DHEA to systemic circulation. Elevated DHEA is then used for synthesis of more potent androgens. Shunting of postabsorbtive glucose from portal to systemic circulation causes early hyperglycemia leading to exaggerated insulin secretion. Insulin bypasses the hepatic metabolism directly entering into the systemic circulation, which results in hyperinsulinemia, then in turn causes late hypoglycemia. Finally, hypothyroxinemia was linked to thyroxin-binding globulin deficiency, which has not been reported in CPSS.

Hereditary hemorrhagic telangiectasia, liver disease and elevated serum testosterone (Osler–Weber–Rendu syndrome): a case report

“…These females had elevated serum testosterone and other downstream androgens in the presence of low DHEAS, as seen in our patient [6]. It is postulated that the mechanism of hyperandrogenemia, could be impaired conversion of DHEA to its inactive sulphate ester DHEAS in the liver, due to bypassing of DHEA to the systemic circulation [6]. This would lead to low DHEAS and elevated DHEA in the circulation.…”

“…However, there have been a few reported cases of elevated serum testosterone in association with porto-systemic shunting in young females [5, 6]. The initial observation was reported in two adolescent girls with congenital porto-systemic shunting, who presented with virilisation and amenorrhea, and had elevated testosterone [5].…”

“…The initial observation was reported in two adolescent girls with congenital porto-systemic shunting, who presented with virilisation and amenorrhea, and had elevated testosterone [5]. More recently, Bas et al [6] reported on two 7-year old girls with congenital portosystemic shunts, presenting with premature pubarche. These females had elevated serum testosterone and other downstream androgens in the presence of low DHEAS, as seen in our patient [6].…”

“…More recently, Bas et al [6] reported on two 7-year old girls with congenital portosystemic shunts, presenting with premature pubarche. These females had elevated serum testosterone and other downstream androgens in the presence of low DHEAS, as seen in our patient [6]. It is postulated that the mechanism of hyperandrogenemia, could be impaired conversion of DHEA to its inactive sulphate ester DHEAS in the liver, due to bypassing of DHEA to the systemic circulation [6].…”

“…This would lead to low DHEAS and elevated DHEA in the circulation. As DHEA is a precursor for the synthesis of more potent downstream androgens such as androstenedione and testosterone, elevated DHEA would lead to elevated serum testosterone and features of hyperandrogenism [6]. …”