Hypopituitarism
Anatomy and Physiology
Hypothalamic-Pituitary Axis
The pituitary gland is divided into:
| Part | Connection to Hypothalamus | Type of Signalling |
|---|---|---|
| Anterior pituitary (adenohypophysis) | Hypothalamo–hypophyseal portal system | Vascular (blood-borne hormones) |
| Posterior pituitary (neurohypophysis) | Direct neuronal connection (axons) | Neural signalling |
Anterior Pituitary – Portal Circulation
Hypothalamic neurons release hormones into blood vessels, not directly into the anterior pituitary:
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Hypothalamic neurons release hormones into the primary capillary plexus
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These hormones travel via the hypophyseal portal veins (situated within the pituitary stalk)
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They reach the secondary capillary plexus in the anterior pituitary
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This stimulates or inhibits anterior pituitary hormone release
Posterior Pituitary – Direct Neural Signalling
Posterior pituitary hormones are synthesised in the hypothalamus, then transported down to the posterior pituitary:
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Hormones are synthesised in hypothalamic neurons
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These hormones travel down axons via the hypothalamo–hypophyseal tract (situated within the pituitary stalk)
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They reach and are stored in the posterior pituitary
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These hormones are directly secreted into the systemic circulation, in the posterior pituitary
Pituitary Gland Hormones
Anterior pituitary hormones
| Hypothalamic Hormone | Action on pituitary | Pituitary Hormone | Target Organ | Main Effect |
|---|---|---|---|---|
| TRH (thyrotropin-releasing hormone) | Stimulatory |
↑ TSH (thyroid stimulating hormone) | Thyroid gland | ↑ T3/T4 |
| CRH (corticotropin-releasing hormone) | ↑ ACTH (adrenocorticotropic hormone) | Adrenal cortex | ↑ Cortisol | |
| GnRH (gonadotropin-releasing hormone) | ↑ LH (luteinising hormone) / FSH (follicle-stimulating hormone) | Ovaries / testes | ↑ Oestrogen, testosterone | |
| GHRH (growth hormone-releasing hormone) | ↑ GH (growth hormone) | Liver | Direct effect and indirect effect via IGF-1 | |
| Somatostatin | Inhibitory |
↓ GH (growth hormone) | n/a | Inhibit GH secretion |
| Dopamine | ↓ Prolactin | n/a | Inhibit prolactin secretion |
It is worth noting that TRH can act on the anterior pituitary to stimulate prolactin secretion. Therefore, hypothyroidism can cause hyperprolactinaemia.
Posterior pituitary hormones
| Hormone | Main site of production | Target | Main Effect |
|---|---|---|---|
| ADH (Vasopressin) | Supraoptic nucleus (of hypothalamus) | Kidney collecting ducts | ↑ Water reabsorption |
| Oxytocin | Paraventricular nucleus (of hypothalamus) | Uterus / breast | Uterine contraction + lactation |
Technically, the posterior pituitary does not synthesise hormones. ADH (vasopressin) and oxytocin are synthesised in the hypothalamus and transported to the posterior pituitary, where the posterior pituitary’s role is to store and release the hormones into the systemic circulation.
Anatomical Position
Location of the pituitary gland: sits in the sella turcica of the sphenoid bone
Key anatomical relations:
| Direction | Structure | Clinical Relevance |
|---|---|---|
| Superior | Optic chiasm | → Bitemporal hemianopia if compressed |
| Inferior | Sphenoid sinus | Transsphenoidal surgical access |
| Lateral | Cavernous sinuses | CN III, IV, V1, V2, VI palsies |
| Anterior | Sphenoid sinus | Surgical relevance |
Hypopituitarism
Definition
Hypopituitarism is defined as the deficiency of 1 or more hormones produced by the pituitary gland, more commonly the anterior pituitary.
Aetiology
Key causes include: [Ref]
| Aetiology | Description |
|---|---|
| Intrasellar / parasellar masses |
See the Pituitary Tumours article for more information (mass effect +/- features of hormone excess) |
| Traumatic brain injury and subarachnoid haemorrhage | Esp. skull-base injuries |
| Pituitary apoplexy | Pituitary apoplexy: infarction of the pituitary gland due to ischaemia and/or haemorrhage
Sheehan syndrome is a specific cause of pituitary apoplexy:
|
| Radiation-induced damage | |
| Infiltrative diseases | Examples include sarcoidosis, haemochromatosis |
| Congenital causes | Examples include Kallmann syndrome (→ GnRH deficiency) |
Clinical Manifestation and Tests
Clinical manifestations of hypopituitarism is highly variable, it depends on the specific pituitary hormone deficiencies and the severity: [Ref1][Ref2]
| Deficient Hormone | Site of production | Key Clinical Features |
|---|---|---|
| ACTH (adrenocorticotropic hormone) | Anterior pituitary | Must not miss, as it can cause adrenal insufficiency / adrenal crisis – see the Adrenal Insufficiency (Hypoadrenalism) article for more information |
| TSH (thyroid-stimulating hormone) | Causes secondary hypothyroidism – see the Hypothyroidism article for more information | |
| GH (growth hormone) |
|
|
| LH (luteinising hormone) / FSH (follicle-stimulating hormone) | Causes hypogonadotropic hypogonadism
|
|
| Prolactin (rare) |
|
|
| ADH (vasopressin) | Hypothalamus | Causes central diabetes insipidus – see the Diabetes Insipidus (DI) article for more information |
| Oxytocin (rare) |
|
Triad of pituitary apoplexy:
- SAH-like features (sudden-onset thunderclap headache, meningism, vomiting, reduced level of consciousness)
- Visual field defects (classically bitemporal hemianopia)
- Ophthalmoplegia
Investigation and Diagnosis
Initial Screening Tests
Basal hormone measurements: [Ref]
- Morning serum cortisol +/- short Synacthen test
- Gonadotropins (LH, FSH) and sex steroids (oestrogen, testosterone)
- IGF-1
- Prolactin
Dynamic Stimulation Tests
There are 2 main stimulation tests: [Ref]
- Insulin tolerance test / glucagon stimulation test (gold standard) – tests both ACTH and GH axes
- Both causes hypoglycaemia, which should stimulates both axes to increase cortisol and GH secretion
- The glucagon stimulation test does not directly cause hypoglycaemia. It first causes hyperglycaemia, followed by delayed insulin-mediated hypoglycaemia
- Short synACTHen test for the adrenal axis assessment
Imaging
1st line: MRI pituitary to identify structural lesions [Ref]
Management
Principles of management center on individualised, axis-specific hormone replacement, aiming to restore physiological hormone levels and minimise symptoms and long-term sequelae. [Ref1][Ref2]
| Affected axis | Management (brief) | Corresponding article |
|---|---|---|
| Adrenal axis |
|
Adrenal Insufficiency (Hypoadrenalism) |
| Thyroid axis |
|
Hypothyroidism |
| Gonadal axis |
Pulsatile GnRH or gonadotropin therapy for fertility induction |
|
| Growth hormone axis |
|
|
| ADH axis |
|
Diabetes Insipidus (DI) |