Turner Syndrome and Panhypopituitarism: Connection and Management
Yes, there is a connection between Turner syndrome and panhypopituitarism, although it is uncommon. Patients with Turner syndrome should be evaluated for pituitary function, especially when presenting with symptoms of hormone deficiencies beyond the expected gonadal dysgenesis.
Diagnostic Connection
- Turner syndrome (complete or partial absence of one X chromosome in a phenotypic female) is associated with multiple endocrine abnormalities, with ovarian failure being the most common, but can also present with panhypopituitarism in rare cases 1
- When a patient with Turner syndrome presents with symptoms such as headache, asthenia, delayed growth beyond expected for Turner syndrome, or hypothyroidism with negative thyroid antibodies, pituitary dysfunction should be suspected 1
- Diagnostic evaluation should include complete assessment of all anterior pituitary hormone axes, as panhypopituitarism occurs in 6-29% of patients with pituitary disorders 2
Clinical Evaluation
Morning laboratory tests should include:
- Thyroid function (TSH, free T4)
- Adrenal function (morning cortisol, ACTH)
- Growth hormone axis (IGF-1)
- Prolactin levels
- Gonadotropin levels (FSH, LH) 2
MRI of the sella with pituitary cuts is essential for all patients with suspected panhypopituitarism to identify structural abnormalities like empty sella 2, 1
Diagnostic criteria for hypopituitarism include ≥1 pituitary hormone deficiency combined with MRI abnormality, or ≥2 pituitary hormone deficiencies with associated symptoms like headache 2
Management Approach
Address adrenal insufficiency first before treating other hormonal deficiencies to avoid precipitating an adrenal crisis 2
Thyroid hormone replacement should be initiated after addressing adrenal insufficiency 2
Growth hormone therapy should be considered, especially in children and adolescents with Turner syndrome who have documented GH deficiency 2, 3
Hormone replacement therapy (HRT) with estrogen is indicated for:
Cardiovascular Considerations
All women diagnosed with Turner syndrome should be evaluated by a cardiologist with expertise in congenital heart disease, regardless of pituitary status 4
Cardiovascular risk factors should be assessed at diagnosis and monitored annually (blood pressure, smoking, weight, lipid profile, fasting plasma glucose, HbA1c) 4
Turner syndrome patients have increased risk of aortic dissection, with most dissections occurring in patients with known risk factors such as bicuspid aortic valve, coarctation of the aorta, or systemic hypertension 4
Imaging of the heart, aorta, and pulmonary veins at the time of diagnosis is valuable due to increased risk of dissection 4
Long-term Monitoring
Regular monitoring of hormone replacement adequacy is necessary, including thyroid function, adrenal function, and metabolic panel 2
If BMD is normal and adequate systemic estrogen replacement is commenced, the value of repeated DEXA scan is low 4
For patients with no risk factors for aortic dissection, re-evaluation of the aorta has been suggested every 5 to 10 years or if clinically indicated 4
Patients with risk factors for aortic dissection should undergo more frequent imaging 4
Clinical Pearls and Pitfalls
Diagnostic pitfall: Hypothyroidism with low TSH in Turner syndrome should raise suspicion for central hypothyroidism due to pituitary dysfunction rather than primary hypothyroidism 1
Treatment pitfall: Initiating thyroid replacement before addressing adrenal insufficiency can precipitate an adrenal crisis 2
Monitoring pitfall: Inappropriately low levels of gonadotropins in a patient with Turner syndrome (who should have elevated FSH/LH due to gonadal dysgenesis) suggests central hypogonadism from pituitary dysfunction 1
Management pitfall: Failure to recognize the need for lifelong hormone replacement in patients with combined Turner syndrome and panhypopituitarism 2, 3