15th September 2024

Hypopituitarism

The pituitary gland is located centrally at the base of the brain, within the sella turcica, a depression in the sphenoid bone. It is connected to the hypothalamus by the pituitary stalk and a fine vascular network. On either side of the gland are the cavernous sinuses, through which pass important neurovascular structures, including the internal carotid arteries and cranial nerves III, IV, V, and VI.

The majority of the blood supply to the anterior pituitary comes from the hypothalamic-hypophyseal portal system, which originates from the superior and inferior hypophyseal arteries. The remaining blood supply comes from the pituitary capsular vessels, which also arise from the superior hypophyseal arteries. Venous drainage occurs through the internal jugular veins via the cavernous and petrosal sinuses.

The anterior pituitary releases several hormones with distinct secretion patterns. Prolactin is secreted in a pulsatile circadian rhythm with approximately 14 pulses per 24 hours, peaking during sleep and, to a lesser extent, in the evening. Growth hormone is also secreted in pulses, primarily at night, and its secretion is influenced by age and sex. LH and FSH (gonadotropins) have a pulsatile secretion that depends on the frequency of GnRH secretion. Thyroid-stimulating hormone (TSH) has a 24-hour pulsatile secretion and can cause cross-reactivity during the first trimester of pregnancy, potentially increasing thyroid hormone release and mimicking hyperthyroidism. ACTH is also released in a pulsatile manner.

The hypothalamic-pituitary-hormonal axis is a complex system which has a central role in maintaining homeostasis. The main anterior pituitary hormone axis is shown below.

Causes of hypopituitarism

Hypopituitarism refers to the partial or complete deficiency of one or more hormones produced by the pituitary gland. It can result from a combination of these hormone deficiencies, which may be caused by primary pituitary disease or hypothalamic disorders that disrupt hypothalamic control of the pituitary.

Clinical features

The clinical features of anterior pituitary deficiencies depend on the type and degree of the hormonal deficits. The most common types of hypopituitarism include GH and gonadotrophin deficiencies, followed by TSH and ACTH at a later stage. Prolactin deficiency is rare and is mainly seen in relation to Sheehan syndrome.

Investigations

Basal and dynamic tests are used to assess the function of the hypothalamic-pituitary-hormonal axis. This includes cortisol, prolactin, TSH, Free T4, LH/FSH, testosterone or oestradiol, IGF-1, 9am Cortisol, and ACTH. Baseline posterior pituitary function should also be assessed (covered in another chapter). Dynamic stimulation tests are used to assess hormone under-secretion, including:

• Insulin tolerance test (ITT) for ACTH and GH reserves
• Glucagon test for GH and ACTH reserves
• GHRH and arginine test for GH reserves
• Short synacthen test for ACTH reserves
• CRH stimulation test for adrenal insufficiency
• TRH stimulation test for T3/T4 reserves (for secondary and tertiary hypothyroidism)

For suspected over-secretion in pituitary disorders, use suppression tests such as:

• Oral glucose tolerance test for GH reserves (used for acromegaly)
• Low dose dexamethasone suppression for cortisol levels (used for Cushing’s syndrome)

For other systemic illnesses: serum ACE levels, ferritin, hCG, and alpha-fetoprotein, and perform MRI of the pituitary for optimal imaging.

Management

The mainstay of management of anterior pituitary hormone deficiency is adequate target hormone replacement and management of the underlying cause. Exceptions are growth hormone replacement in adults and when fertility is required (GnRH therapy is given instead of testosterone or oestrogen).

Patients with ACTH deficiency need glucocorticoid replacement only and do not need mineralocorticoid in contrast to patients with primary adrenal disease. GH is replaced in adults when symptomatic, affecting the quality of life as compared to children where regular replacement is required for growth. Thyroid hormone replacement-in pituitary disease, thyroid replacement is monitored via clinical and Free T4 levels as TSH measurement cannot be used to assess adequate replacement due to the TSH deficiency.

Pituitary apoplexy

Haemorrhage directly into the pituitary gland, known as pituitary apoplexy, tends to occur in individuals with a preexisting pituitary adenoma. Patients typically experience a sudden headache, diplopia, and hypopituitarism. Urgent MRI is required for diagnosis and treatment consists of initial steroid replacement and neurosurgical evaluation. Additional hormone replacement may be necessary, depending on the clinical picture.

References

• Snyder P, Martin K. UpToDate [Internet]. Cooper D, editor. UpToDate. Available from: https://www.uptodate.com/contents/causes-of-hypopituitarism
• Chung TT, Monson JP. Hypopituitarism. [Updated 2022 Nov 27]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278989/