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The pituitary is the ‘master controller’ of hormone function in the body, converting signals from the brain and hypothalamus to actions via hormones.

The pituitary normally sits in the sella turcica at the base of the middle cranial fossa (Fig 29.1). It is covered by a dural layer known as the diaphragma sella. The pituitary is joined to the hypothalamus by the infundibulum or pituitary stalk, in front of which sits the optic chiasm. The sella turcica is bounded laterally by the cavernous sinuses and their contents, and the sphenoid sinus antero-inferiorly. The anterior pituitary is embryologically derived from the posterior pharynx and secretes prolactin follicle-stimulating hormone (FSH), luteinising hormone (LH), growth hormone (GH), thyrotropin-stimulating hormone (TSH) and adrenocorticotrophic hormone (ACTH) in response to trophic-releasing hormones from the hypothalamus via a portal blood flow system. The posterior pituitary secretes oxytocin and vasopressin under neural control from the hypothalamus.


Tumours in the pituitary are common and have been found to occur in around 10% of people in autopsy studies.1 Various series have reported rates of up to 24%. With the high background rate of pituitary masses seen on MRI, clinical questions about how to proceed are likely to occur. Unless the brain is imaged for another reason, it is more prudent to have a clinical diagnosis and confirmatory tests of a pituitary disorder before requesting a CT or MRI of the pituitary.

Tumours of the pituitary may be developmental cysts, blood or infarcted tissue, physiological hyperplasia or adenomas.

Adenomas may be functioning or non-functioning. Physiological effects may be excess autonomous secretion of hormones or trophic hormones, loss of normal pituitary function or mass effects that include compression of nearby structures such as the optic chiasm.

Tumours smaller than 10 mm in size are called microadenomas, and those bigger than 10 mm, macroadenomas. Compressive effects of a pituitary tumour normally occur when the adenoma grows to > 10 mm and enlarges beyond the pituitary fossa. Common symptoms of a mass effect are headaches and loss of peripheral vision that correlates with a bitemporal hemianopia as the optic chiasm is compressed.

As an adenoma grows, there may be loss of function of the normal anterior pituitary in a typical order. The mnemonic: ‘Go Looking For That Adenoma’ is a good aide memoire for the order of loss of pituitary function:

Diagnostic approach

The most important thing is that the diagnosis of a pituitary hormone-stimulated excess or deficiency is made, or at least suspected, and then the pituitary may be imaged. Tumours are sometimes found when a CT head or MRI brain is performed for another reason. In this case, careful history and examination needs to be done, and then testing for any anterior pituitary hormone deficiencies or excesses may be done.

Tumours are defined by their size and secretion of hormones. Tumours do not tend to invoke a mass-related loss of function of other anterior pituitary hormones until they tend toward macroadenomas. The exception to this is a prolactinoma, which will suppress the gonadotrophs in a normal physiological way even when it is a microprolactinoma.

Prolactinomas tend to produce prolactin in a linear relation to their size. Macroadenomas therefore tend to produce levels of prolactin greater than 10 times the upper limit of the reference range. Microadenomas tend to produce levels of prolactin from 1–10 times the upper limit of normal. Other causes of prolactin in this range include medications with a dopamine antagonistic effect, such as antipsychotics and antiemetics. Stress may cause a transient increase in prolactin, as will physical causes such as nipple stimulation and lesions that affect the T4 dermatome, including Varicella zoster. Masses that result in compression or loss of function of the pituitary stalk also limit the inhibitory signals from the hypothalamus and result in microadenoma-level hyperprolactinaemia.


Target the examination to the symptoms and manifestations of hormone excesses or deficiencies as outlined in Table 29.1. Check for galactorrhoea as well as back and skin lesions in patients suspected with hyperprolactinaemia. Galactorrhoea from one breast in the absence of hyperprolactinaemia requires careful examination to ensure that there is no local breast pathology. Always check visual fields to confrontation.



In a pituitary mass, checking paired trophic hormones and their target hormones is essential for proper interpretation. Check ACTH and cortisol at around 8–9 am, together with FSH, LH and testosterone (oestrogen in females), which also has a diurnal variation, with higher levels in the morning, TSH and thyroxine (T4), prolactin (with dilution in macroadenomas), GH and insulin-like growth factor 1 (IGF-1). Non-functioning adenomas tend to produce higher levels of alpha-1 glycoprotein subunit, which may be requested on a sample of serum. Be aware that ACTH in particular degrades quickly, and so informing the laboratory beforehand of an impending test can help ensure it is put on ice and sent to the central laboratory quickly.

The above are static tests. If both results are normal, beware of the inappropriate levels such as a T4 at the lower limit of normal, with a lower limit of normal TSH (inappropriately normal).

If there are any concerns, dynamic tests may be ordered, although these are often ordered by a specialist and/or in a hospital environment. Of the dynamic test, the oral glucose tolerance test (OGTT) to suppress GH to < 1.0 ng/mL is the only one that is reliable and may safely be done as an outpatient. Twenty-four hour urinary free cortisol and 1 mg overnight dexamethasone suppression tests may also be performed as an outpatient, to help with the investigation of cortisol excess. If an excess is confirmed, then a high-dose dexamethasone suppression test will help delineate whether the problem is Cushing’s disease or ectopic ACTH production.

Integrated management


Acromegaly is a condition of monoclonal growth of pituitary somatotrophs that produces excess growth hormone in a non-regulated way. It has a prevalence of around three per million.2

GH is normally secreted in a diurnal and metabolic fashion, with pulsatile release that is highest during sleep. Amino acids and ghrelin from the gut are also stimuli to its release via the hypothalamus.

GH stimulates the production of IGF-1 and IGFBP-3 (insulin-like growth factor binding protein-3) on binding to the receptors in the liver. There are some direct effects on the cartilage but, other than that, the majority of the physiological effects of GH are mediated via IGF-1. The liver’s ability to produce IGF-1 in response to GH is blunted in liver disease, hypothyroidism and poorly controlled diabetes mellitus. Interestingly, malnutrition reduces IGF-1 production, and obesity inhibits GH pulses from the pituitary.

Integrated management

See Fig 29.2 for an overview of management.


Hypopituitarism may be complete (pan-) or partial. It may be congenital, acquired or iatrogenic.

Congenital problems are many and rare, and such things as PIT-1 gene mutations cause a loss of lactotrophs (prolactin), thyrotrophs (TSH) and somatotrophs (GH). Others, such as Kallmann’s syndrome, result in loss of the gonadotrophs and a normal male phenotype but hypogonadotrophic hypogonadism and a degree of olfactory deficit.

Acquired hypopituitarism may occur due to problems such as trauma affecting the pituitary stalk (infundibulum), apoplexy or infarction in Sheehan’s syndrome. Other issues such as lymphocytic hypophysitis are being increasingly recognised with higher-teslar MRI machines. Infections and inflammatory lesions such as sarcoid and histiocytosis may affect the pituitary, as well as intra- and extrasellar masses.

Iatrogenic causes include radiation-associated pituitary damage or surgical complication after attempted removal of a macroadenoma.

Lastly, hypopituitarism can be secondary to hypothalamic disease.


ACTH TSH   ADH/vasopressin

Integrated management


Located generally behind the thyroid gland are the four parathyroid glands, which have the role of producing parathyroid hormone (PTH). PTH is the main controller of calcium levels within the blood and bones, and this of course has important implications for neuromuscular function.


Extracellular calcium is a tightly controlled electrolyte. Significant symptoms, including life-threatening conditions, occur when control is lost and the levels of calcium in the body go outside the tightly controlled range. The largest store of calcium within the body is in the bones, but calcium is stored within skeletal and cardiac muscle, and within the neuronal signalling and neuromuscular junctions.

The most common symptoms of hypercalcaemia are the classic ‘stones, bones, moans and groans’ of kidney stones, bone pains, mood changes including depressive symptoms and abdominal pains including constipation. Polyuria and dehydration can occur secondary to high serum calcium. The most common cause for congenital hypercalcaemia is familial hypocalciuric hypercalcaemia. The most common acquired causes of hypercalcaemia are hyperparathyroidism and malignancy. A useful thought map to think about acquired hypercalcaemia is to think about PTH-dependent and PTH-independent causes of hypercalcaemia (see Fig 29.3).


Extracellular calcium is normally controlled very tightly by two interrelated hormones, namely parathyroid hormone (PTH) and vitamin D. There is a sigmoidal inverse relationship between serum calcium levels and PTH levels, such that a decrease in serum calcium results in increased PTH and vice versa.

Familial hypocalciuric hypercalcaemia is a congenital variation in the sensitivity of the calcium-sensing receptor, with a reduced sensitivity to serum calcium and so a higher set point of serum calcium at which the PTH is turned down. Serum calcium is high, as is PTH, but urine 24-hour calcium excretion is low.

Milk–alkali syndrome is less common now that histamine receptor antagonists and proton pump inhibitors are the mainstay treatment of hyperacidity syndromes of the stomach. The use of antacids together with the ingestion of milk products results in increased absorption and mild hypercalcaemia. While there has been a reduction in the presentation of milk–alkali syndrome from these less-used drugs, there have been a number of case reports of similar presentations in those using large doses of calcium carbonate, which provides both calcium and alkali. High calcium level together with high bicarbonate and perhaps some renal impairment should prompt the GP to ask about calcium carbonate intake.

PTH-dependent hypercalcaemia can be due to primary hyperparathyroidism, less commonly secondary hyperparathyroidism, or tertiary hyperparathyroidism. Secondary hyperparathyroidism often does not result in hypercalcaemia alone, as it is an appropriate response to maintain calcium levels. This occurs in the situation of vitamin D deficiency, where high parathyroid levels maintain serum calcium when vitamin D levels are insufficient to provide enough gut and renal absorption to do so. Primary hyperparathyroidism may be due to a parathyroid adenoma, or adenomas on their own or in the setting of MEN1 syndrome of pituitary tumours, hyperparathyroidism and pancreatic tumours, or MEN2 with medullary thyroid cancer and phaeochromocytoma. Parathyroid adenomas are most commonly sporadic and not part of another syndrome, and are mostly single-gland adenomas. Less commonly, PTH-secreting thymus tumours can produce the parathyroid hormone excess. Tertiary hyperparathyroidism is thought to occur through long-standing secondary hyperparathyroidism, which then causes irreversible parathyroid gland hyperplasia and autonomous function.

PTH-independent causes of hypercalcaemia are usually due to excesses in active vitamin D, or lytic lesions of the bone. The far less common production of PTHrp (PTH-related protein) is usually associated with squamous cell carcinomas, or renal, bladder, breast or ovarian cancers. The conditions that result in excess active vitamin D (1,25-dihydroxy vitamin D) are excess intake of calcitriol, or granulomatous diseases such as sarcoid, tuberculosis and lymphoma, both non-Hodgkins and Hodgkins. In these conditions the macrophages in the granulomata convert the inactive vitamin D to active vitamin D without the need for PTH, which normally carries this out by stimulating the 1-alpha-hydroxylase enzyme in the kidneys.

Other causes such as multiple myeloma and breast cancer are the two more common malignancies that can lead to lytic bone lesions and uncontrolled release of calcium into the extracellular fluid, independently of a suppressed PTH level.