How to manage Attention Deficit Hyperactivity Disorder (ADHD) symptoms in a female patient with Turner syndrome?

Managing ADHD Symptoms in Patients with Turner Syndrome

Treat ADHD in Turner syndrome patients using standard ADHD management protocols, starting with cognitive behavioral therapy and psychoeducation for mild-to-moderate symptoms, and adding stimulant medications (methylphenidate or amphetamines) or non-stimulants (atomoxetine) for moderate-to-severe symptoms, while maintaining heightened cardiovascular monitoring given the elevated cardiac risk inherent to Turner syndrome. 1, 2

Initial Assessment and Screening

• Screen for ADHD using the Adult ADHD Self-Report Scale (ASRS-V1.1), with a positive screen requiring 4 or more items marked "often" or "very often" out of 6 questions 3
• Assess functional impairment using the Weiss Functional Impairment Rating Scale-Self (WFIRS-S) 4, 3
• Rule out conditions that mimic ADHD symptoms, including depression, anxiety disorders, thyroid dysfunction (common in Turner syndrome), and sleep disorders 4, 5
• Evaluate for common Turner syndrome-associated comorbidities that may worsen ADHD symptoms: hypothyroidism (present in up to 30% of patients), hearing loss, and psychological distress 5, 6

Non-Pharmacologic First-Line Treatment

For mild-to-moderate ADHD symptoms, begin with non-pharmacologic interventions before considering medications. 1, 3

• Provide psychoeducation about ADHD and its management in the context of Turner syndrome 1, 4
• Implement cognitive behavioral therapy (CBT) adapted for ADHD, which is the most extensively studied and effective psychotherapy, targeting executive functioning skills including time management, organization, planning, emotional self-regulation, and impulse control 1, 7, 3
• Offer self-management strategies and coaching to develop compensatory organizational skills 1, 4
• Consider mindfulness-based interventions and dialectical behavior therapy as adjunctive approaches 1

Pharmacologic Management

For moderate-to-severe ADHD symptoms that impair daily functioning, pharmacotherapy is required even in Turner syndrome patients. 1, 3

Stimulant Medications (First-Line Pharmacotherapy)

• Initiate methylphenidate or amphetamine derivatives as first-line pharmacologic treatment, as these have the strongest evidence base for ADHD efficacy 1
• Note that females may show superior response at 2.5 hours post-dosing with stimulant medication but inferior response after 12 hours compared to males, suggesting that women may benefit from different dosing regimens or shorter-acting formulations 1
• Consider intermittent use or dose adjustments based on functional demands and symptom patterns 1

Non-Stimulant Alternatives

• Consider atomoxetine (initiated at 40 mg daily, increased after minimum 3 days to target dose of 80 mg daily, with maximum 100 mg daily) for patients who cannot tolerate stimulants or have contraindications 2
• Atomoxetine should be initiated at 0.5 mg/kg daily and increased after minimum 3 days to target of 1.2 mg/kg daily in adolescents under 70 kg 2
• Consider bupropion as an alternative, particularly for patients with co-occurring depression, though recognize it is not as efficacious as stimulants for ADHD treatment 1

Critical Turner Syndrome-Specific Cardiovascular Monitoring

Given the significantly elevated cardiovascular risk in Turner syndrome, implement enhanced cardiac surveillance when prescribing ADHD medications. 1, 5

• Ensure all patients with Turner syndrome have undergone comprehensive cardiovascular evaluation by a cardiologist with expertise in congenital heart disease before initiating ADHD medications 1, 5
• Obtain baseline magnetic resonance angiography in addition to echocardiography to evaluate for bicuspid aortic valve (present in 15-30% of patients), coarctation of the aorta, aortic root dilatation, and elongation of the transverse aortic arch 1, 5, 6
• Monitor blood pressure at every visit, as hypertension is common in Turner syndrome (found in 26% of previously undiagnosed adult patients) and can be exacerbated by stimulant medications 1, 6
• Calculate ascending aortic size index (ASI - ratio of aortic diameter in mm to BSA in m²) or aortic height index (AHI - ratio of aortic diameter in mm to height in m) to account for smaller body size in Turner syndrome patients 1
• Reassess cardiovascular status if increasing ADHD medication doses, particularly stimulants which can elevate blood pressure and heart rate 2

Management of Common Comorbidities

Address co-occurring conditions that frequently accompany both ADHD and Turner syndrome, as untreated comorbidities will undermine ADHD treatment effectiveness. 1, 5, 6

• Screen and treat thyroid dysfunction, as subclinical hypothyroidism was newly diagnosed in 22% of adult Turner syndrome patients in standardized screening and can worsen attention and executive function 6
• Evaluate and manage hearing loss, which warrants hearing aids in approximately 5% of adult Turner syndrome patients and can mimic or exacerbate inattention symptoms 6
• Recognize that approximately 10% of adults with recurrent depression and/or anxiety have comorbid ADHD, and treatment of depression/anxiety will likely be inadequate without addressing the underlying ADHD 3
• Screen for glucose intolerance (found in 8% of previously undiagnosed adult Turner syndrome patients) and dyslipidemia (found in 35% of patients), as metabolic dysfunction can worsen cognitive symptoms 6

Ongoing Monitoring and Adjustment

• Reassess ADHD symptom severity and functional impairment at regular intervals using validated scales 4, 3
• Monitor for medication adherence, a common issue in adolescents and adults with ADHD 1
• Adjust medication dosing based on response, tolerability, and changes in functional demands 1, 2
• Continue cardiovascular risk factor monitoring at least annually, including blood pressure, weight, lipid profile, fasting glucose, and HbA1c 1
• Maintain estrogen replacement therapy in Turner syndrome patients, as adequate estrogen is important for bone health, cardiovascular protection, and may influence cognitive function 1

Important Caveats and Pitfalls

• Do not delay ADHD treatment due to Turner syndrome diagnosis alone - the risks of untreated ADHD (impaired functioning, increased accident risk, comorbid depression/anxiety) must be weighed against medication risks 1, 3
• Avoid assuming all attention problems are due to ADHD - Turner syndrome patients may have nonverbal learning disorders or psychosocial difficulties that require different interventions 5, 8
• Do not overlook the need for comprehensive educational and psychological evaluation in Turner syndrome patients with ADHD, as they may have specific learning disabilities requiring specialized educational support 5, 8
• Recognize that atomoxetine carries a black box warning for suicidal ideation in children and adolescents (0.4% risk vs. 0% with placebo), requiring careful monitoring especially during treatment initiation 2
• Be aware that many adult women with Turner syndrome lack adequate medical follow-up (30% in one study) and estrogen replacement (15% lacking therapy), necessitating comprehensive care coordination 6