Pituitary tumours are tumours, both benign and malignant, that involve the pituitary gland. Benign tumours are pituitary adenomas while malignant tumours are pituitary carcinomas (which are rare).
🦴 Anatomy and physiology
The pituitary gland, or hypophysis, is a pea-sized gland that sits in the sella turcica (pituitary fossa) of the sphenoidal bone. It is suspended from the hypothalamus by the infundibilum (pituitary stalk). Together the hypothalamus and pituitary form the hypothalamic-pituitary axis (HPA). The HPA is the control centre for endocrine function within the body with many hormones being regulated.
The pituitary gland has 2 parts - an anterior and posterior portion.
Let’s look at both of these in more detail, followed by a little look at the hypothalamus:
- Anterior pituitary
The anterior pituitary, also known as the adenohypophysis, forms embryologically from glandular tissue as opposed to neural tissue. Therefore it does not have its own innervation and instead it is stimulated by the hypothalamic hormones via the hypophyseal portal system. The superior hypophyseal artery (a branch of the internal carotid artery) provides the arterial supply to the anterior pituitary. It then forms the primary hypophyseal plexus with capillaries and portal veins.It is at the primary plexus where the hypothalamic hormones are secreted. This primary plexus drains into a secondary hypophyseal plexus on the anterior pituitary to activate the troph cells of the anterior pituitary to secrete the hormones into our bloodstream.
- Posterior pituitary
- Hypothalamus
The posterior pituitary, also known as the neurohypophysis, is the neural portion of the pituitary gland. It is innervated directly by magnocellular neurons located within the anterior (supraoptic) and paraventricular regions of the hypothalamus. These axons release anti-diuretic hormone (ADH) and oxytocin into the systemic circulation.
The hypothalamus controls the anterior pituitary through these neuronal projections or through the venous plexuses. Both systems receive hormones produced by the hypothalamus. Let’s look a little further at these hypothalamic hormones.
Hypothalamic hormones | Anterior pituitary hormones |
Growth hormone releasing hormone (GHRH) | Growth hormone (GH) |
Thyrotrophin releasing hormone (TRH) | Thyroid stimulating hormone (TSH) |
Corticotrophin releasing hormone (CRH) | Adrenocorticotrophic hormone (ACTH) |
Gonadotropin releasing hormone (GnRH) | Luteinising hormone (LH) and follicle stimulating hormone (FSH) |
Prolactin releasing hormone | Prolactin |
Somatostatin (also known as growth hormone inhibiting hormone) | Inhibits GH secretion |
The anterior/supraoptic and paraventricular regions of the hypothalamus produce ADH and oxytocin which are released to the posterior pituitary where they are stored.
🔢 Classification
Broadly, we can classify pituitary tumours as benign (adenomas) and malignant (carcinomas).
- Pituitary adenomas - these are benign tumours. The WHO classification classifies these adenomas into their subtypes based on their cell lineage:
- Lactotroph adenomas (also known as prolactinomas)
- Somatotroph adenomas
- Thyrotroph adenomas
- Corticotroph adenomas
- Gonadotroph adenomas
- Non-functional (null cell) adenomas
- Plurihormonal adenomas (pituitary tumour secreting 2 or more hormones).
- Pituitary carcinomas - these are malignant tumours of the pituitary and are very rare, mostly occurring in elderly patients.
We will predominantly be looking at pituitary adenomas and looking a little further at acromegaly (as the other types of adenomas are covered separately):
Pituitary adenomas make up 15% of intracranial tumours, making them the second most common intracranial tumour (after meningiomas).
⚠️ Risk factors
- Multiple endocrine neoplasia 1 (MEN-1) - multiple tumours throughout the endocrine system, most commonly in the parathyroid, pancreas and pituitary.
- Carney complex (CNC)- a rare genetic disorder characterised by multiple neoplasia (mainly in the skin, pituitary, connective tissue (myxomas) and heart.
- Familial isolated pituitary adenomas - hereditary condition with an autosomal dominant pattern of inheritance. Unlike MEN-1 and CNC, it solely affects the pituitary.
🔢 😷 Classification and presentation
We previously mentioned the WHO classification based on the cell type, but let’s look at an alternative way of classifying these tumours - functional versus non-functional:
- Functional adenomas - adenomas that cause hormonal hypersecretion. They may cause different syndromes with their own presentations depending on the cell type involved:
- Prolactinoma - due to a lactotroph adenoma.
- Hyperthyroidism - due to a thyrotroph adenoma.
- Cushing’s syndrome - due to a corticotroph adenoma.
- Acromegaly - due to a somatotroph adenoma.
💡 All of these mentioned conditions will be covered separately in-depth, except for acromegaly which will be covered below.
- Non-functional adenomas - these do not cause hormonal hypersecretion and are deemed clinically non-functional pituitary adenomas (CNFPAs). They are often asymptomatic early on and identified incidentally and are therefore known as pituitary incidentalomas. If they grow large enough, they may cause symptoms such as:
- Pituitary dysfunction
- Hypothalamus dysfunction
- Neurological symptoms - especially visual issues such as bitemporal hemianopia.
Other symptoms include:
- Headache - persistent and localised to the centre of the head.
- Visual field defects - due to compression of the optic chiasm.
🔍 Investigations
- 🏆 Brain MRI - gives visualisation of the tumour and its location.
- Visual field assessment - to see if there is compression of the optic chiasm.
- Hormonal tests - to assess which cell lineage the tumour derives from.
🧰 Management
- 🥇 Trans-sphenoidal hypophysectomy - this is the primary management option. It involves gaining access to the pituitary gland via the sphenoidal sinus and then removing the tumour.
- Radiotherapy - this is implemented in situations where it is not possible to remove the entirety of the tumour or with recurrence.
Certain functional adenomas may be managed with medications targeting the overproduction of the hormone:
- Dopamine agonists (bromocriptine and cabergoline) - as dopamine antagonises prolactin production it can be used in cases of prolactinoma.
- Somatostatin analogues (octreotide) - these block excessive growth hormone.
Acromegaly is a rare, chronic disease caused by excessive secretion of growth hormone (GH), usually due to a pituitary somatotroph adenoma. Other less common causes include a hypothalamic over-secretion of GHRH, ectopic release of GHRH, or a primary pituitary hyperplasia.
If onset was in childhood, it would be referred to as gigantism.
The key difference between gigantism and acromegaly is the age of onset: gigantism occurs before epiphyseal plate closure, leading to excessive linear growth, while acromegaly occurs after plate closure, causing enlargement of bones and soft tissues.
Pathophysiology
The growth hormone pituitary axis involves the hypothalamus, which releases growth hormone releasing hormone (GHRH) stimulating the pituitary gland to release GH.
Excess GH results in excess production of insulin-like growth factor 1 (IGF-1). The IGF-1 receptor is distributed on a wide variety of tissues, and excess stimulation results in excessive growth of these tissues.
Excess GH also results in increased gluconeogenesis, lipolysis, and insulin resistance.
😷 Presentation
- Face
- Coarsening of facial features
- Prominent jaw
- Prognathism - protrusion of the jaw.
- Hands
- Spade-like, large hands
- Diabetic finger-prick marks
- Sweaty
- Thick skin with large pores
- Skin
- Increased skin thickness
- Skin tags
- Acanthosis nigricans
- Increased sweating
- Carpal tunnel syndrome - due to IGF-1-mediated soft tissue hypertrophy
- Arthropathy - joint pain and dysfunction
- Snoring - due to IGF-1-mediated soft tissue hypertrophy leading to macroglossia.
- Sexual function changes - reduced libido, oligomenorrhoea, infertility, galactorrhea, ED
- Hypertension
🔍 Investigation
We should begin with a physical examination and clinical history.
- Bloods
- 🥇 IGF-1 - raised.
- 🏆 Oral glucose tolerance test (OGTT) - this is the gold-standard test. Normally glucose suppresses growth hormone. However, in acromegaly, there is lack of suppression during an OGTT.
- Random serum growth hormone - raised.
- Imaging and other tests (such as polysomnography in cases of obstructive sleep apnoea, or colonoscopies due to the risk of colorectal cancer).
🧰 Management
- 🏆 Surgery - to remove the adenoma is the primary treatment of choice.
- 🥇 Trans-sphenoidal hypophysectomy
- 🥈 Transfrontal hypophysectomy
- Medical management - if surgery is contraindicated or the mechanism is not due to a pituitary adenoma, or if the presentation is refractory to surgery.
- 🥇 Somatostatin analogues (octreotide, lanreoride) - suppress growth hormone release.
- Growth hormone antagonists (pegvisomant)
- Dopamine agonists (bromocriptine, cabergoline)
- Follow up:
- Monitor for bowel malignancy and cardiac failure (with colonoscopy and echocardiography) - these often have to continue even after the post-operative period, since the sequelae can be long term.
- To detect recurrence:
- Serial IGF-1s/growth hormone
- Prolactin (concomitant prolactin release in the adenoma occurs in 30% of cases)
- Visual field assessments
- ECGs
- MRI scans of pituitary