Hypopituitarism

Hypopituitarism is an endocrine disorder characterised by a deficiency in ≥1 pituitary hormone. It can present variably depending on the hormones that are affected. Panhypopituitarism occurs when all the hormones secreted by the pituitary are reduced.

🦴 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

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.

• Hypothalamus

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.

🔢 Pathophysiology and classification

We can classify hypopituitarism into primary and secondary hypopituitarism. By doing so we can discuss some of the aetiological factors that contribute to hypopituitarism:

• Primary hypopituitarism - this is due to disorders of the pituitary gland. It may be due to factors such as:
• Congenital - due to genetic mutations, most commonly in the PROP1 gene. It may also be associated with congenital syndromes such as septo-optic dysplasia (previously de Morsier syndrome).

Septo-optic dysplasia is when there is malformation of the anterior portion of the brain during development which results in optic nerve hypolasia, abnormalities of the septum pellucidum, pituitary hypolasia/hypopituitarism.

• Tumours - the most common tumour in children is a craniopharyngioma while the most common in adults is a pituitary adenoma. We will be discussing this further in the dedicated topic on pituitary tumours.
• Autoimmune (leukocytic) hypophysitis
• Infarction and vascular - aneurysms of the carotid arteries, Sheehan’s syndrome (postpartum pituitary necrosis), pituitary apoplexy (sudden development of a haemorrhage or a pre-existing pituitary adenoma).
• Infection - due to pituitary abscesses, meningitis, tuberculomas and fungal pituitary disease (due to AIDS).
• Iatrogenic - after pituitary surgery, radiotherapy or chronic opiate use.
• Infiltrative - such as haemochromatosis, sarcoidosis, and leukocytic hypophysitis.
• Secondary hypopituitarism - this is hypopituitarism caused by structures around the sella turcica (parasellar structures) such as the hypothalamus and cavernous sinus, for example.
• Hypothalamic tumours
• Hypothalamic neurohormonal deficiencies
• Traumatic brain injuries

😷 Presentation

The presentation is dependent on the hormones that are deficient. Most commonly, GH is lost first, then → GnRH → TSH and ACTH.

If ADH deficiency is present, it is more likely a lesion of the pituitary stalk and hypothalamus.

So what are the symptoms of these hormone deficiencies?

• TSH deficiency causes hypothyroidism.
• ADH deficiency causes diabetes insipidus.
• Prolactin deficiency causes lactational difficulties.

Other symptoms that may indicate an underlying cause:

• Headaches - secondary to a raised intracranial pressure from a space-occupying lesion or due to pituitary apoplexy.
• Bitemporal hemianopia - may indicate a pituitary macroadenoma.

🔍 Investigations

1. MRI or CT
2. Pituitary hormone levels
3. Target hormone levels - such as FT4, testosterone (in men) and oestradiol (in women), cortisol levels.

🧰 Management