Bipolar disorder in Pendred syndrome: A case report of two siblings

To the Editor

Pendred syndrome was first described by British practitioner Vaughan Pendred (1896), and is an autosomal recessive disorder characterized by congenital bilateral sensorineural deafness and goitre. Neuropsychiatric symptoms such as mood disturbances and cognitive impairment are common among patients with thyroid disorders. We present the case of two siblings suffering from Pendred syndrome who developed bipolar disorder.

Two sisters, presently aged 22 years and 20 years respectively, born out of consanguineous marriage, deaf and mute since childhood, started developing neck swelling at the age of 14 and 12 years, respectively. Five years later, surgical consultation was undertaken as both developed respiratory difficulty due to the swelling. Multinodular goitre with euthyroid state was diagnosed.

Both sisters underwent subtotal thyroidectomy with smooth post-operative recovery. Congenital bilateral deafness along with goitre in both siblings led to clinical diagnosis of Pendred syndrome. A year after surgery, both sisters developed symptoms of mania within 2–3 days of each other. Thyroid profile revealed hypothyroidism in both siblings. Thyroxine (50 μg/day) and olanzapine (20 mg/day) were prescribed. Both reached premorbid status in 6–7 weeks. They presented again to psychiatry OPD after 2 years, with the older sister showing symptoms of moderate depression and the younger sister displaying manic features without psychotic symptoms. The onset of illness was within 3–4 days of each other. Thyroid status revealed hypothyroidism in both siblings.

Bipolar depression was treated with sodium valproate (800 mg/day) and fluoxetine (20 mg/day) and mania with sodium valproate (800 mg/day) and olanzapine (10 mg/day) along with thyroxine supplement (50 μg/day). The symptoms remitted within 6 weeks.

The above cases were unique in two aspects. Firstly, the affective symptoms started almost simultaneously in both sisters in both episodes. The symptoms of goitre also developed simultaneously in both siblings. Secondly, to the best of our knowledge, there have been very few cases reported of Pendred syndrome along with florid psychiatric symptoms.

Whether the affective episodes are directly related to the underlying genetic abnormality or secondary to thyroid dysfunction is not clear. However, with thyroid dysfunction, it is expected that significant numbers of patients with Pendred syndrome may develop neuropsychiatric symptoms.

Various researchers have hypothesized that mood symptoms secondary to thyroid abnormalities may be mediated by changes in neurotransmitters with T3 effectiveness as an antidepressant stemming from augmentation of beta adrenergic activity (Whybrow and Prange, 1981) to modulation of serotonergic, GABA and dopaminergic systems accounting for psychiatric manifestations in patients with thyroid dysfunction (Manzano et al., 2007).