This 19 year old girl has Hereditary haemorrhagic telangiectasia with chronic liver disease and pulmonary AVM. She has a masculine appearance due to impaired sulfation of dehydroepiandrosterone (DHEA) as a result of portocaval shunting.
Hereditary hemorrhagic telangiectasia—HHT (Osler–Weber–Rendu syndrome) was first described in the nineteenth century as a familial disorder causing nose bleeds, gastrointestinal bleeding and abnormal vascular structures. It is inherited as an autosomal dominant trait. A diagnosis of HHT could be made based on Curacao’s criteria, which are; Spontaneous recurrent epistaxis, multiple telangiectases at characteristic sites such as lips, oral cavity, fingers, nose, visceral lesions such as gastrointestinal telangiectasia, pulmonary AVM, hepatic AVM, Cerebral AVM and spinal AVM, a family history of a first degree relative with HHT. The presence of three criteria makes it a definite diagnosis of HHT, while two make the diagnosis possible. Our patient had spontaneous recurrent epistaxis, visceral AVM in the form of pulmonary AVM and telangiectasia in the oral mucosa. There was no family history of HHT. Based on these three criteria a definitive diagnosis of HHT was made [1]. The diagnosis was made at 19 years of age as the telangiectasia of the oral mucosa appeared only at nineteen years.
Spontaneous recurrent nose bleeds from telangiectasia of the nasal mucosa are the most common manifestations of HHT and occurs in about 95% [2]. Intervention for epistaxis should be considered if there is anaemia attributable to nose bleeding or if the frequency and duration of bleeding interferes with normal activities [2]. Our patient required no treatment as the epistaxis was self-limiting. Telangiectases of the skin and buccal mucosa also occur in about 95% of patients, typically presenting later in life than epistaxis [2]. It usually presents in about the third decade of life and gradually increases in number and size. They mostly occur in the face, lips, tongue, buccal mucosa and finger tips and can occur elsewhere. Our patient had telangiectases over the oral mucosa and conjunctivae.
Pulmonary AVMs are thin walled abnormal vessels that replace normal capillaries between pulmonary arterial and venous circulation. In one study 37% of patients with HHT demonstrated pulmonary AVM on high resolution computed tomography (CT). The safest method for treatment is transcatheter embolisation. Since our patient had bilateral diffuse pulmonary AVM conservative management was planned. Cerebral AVMs occur in approximately 10% of patients with HHT [2]. They can cause headache, seizures, ischaemia of the surrounding tissue, or haemorrhage. Our patient did not have cerebral involvement.
Hepatic involvement is variable in HHT. In one study only 8% showed symptomatic involvement [2]. In HHT, the predominant liver involvement seen was shunting of blood from hepatic artery to hepatic veins with shunting of metabolites from portal circulation to systemic circulation. A shunt from hepatic artery to portal vein leads to portal hypertension and increased blood flow can lead to nodularity of the liver due to increased deposition of fibrous tissue. The liver undergoes nodular transformation also known as “pseudo-cirrhosis” [3]. In our patient there was no vascular malformation of the liver however nodular hyperplasia was seen. She did not undergo liver biopsy as there is a risk of bleeding. Liver transplantation is currently the only curative option for symptomatic liver disease in HHT. Except for hepatocellular and biliary necrosis which requires urgent liver transplantation consensus on the most appropriate timing of the transplantation is lacking [4].
To our knowledge, elevated serum testosterone levels have not previously been reported in females with HHT. 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]. 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].
This is a classical case of HHT with hyperandrogenaemic features. This probably could be the first reported case with hyperandrogenaemia secondary to hepatic AVM leading to shunting of blood leading to underclearance of proandrogenic metabolites from the circulation.
