chapter 29 Endocrinology
PITUITARY DISORDERS
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.
PITUITARY TUMOUR
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.
Aetiology
Diagnostic approach
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.
Examination
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.
ACROMEGALY
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
Investigations
Integrated management
See Fig 29.2 for an overview of management.
HYPOPITUITARISM
Hypopituitarism may be complete (pan-) or partial. It may be congenital, acquired or iatrogenic.
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.
Lastly, hypopituitarism can be secondary to hypothalamic disease.
Diagnostic approach
Screening for hypopituitarism should be thought of in those with developmental problems such as:
or those with:
or those who have had pituitary surgery or cranial radiation.
History
Depending on the suspected aetiology, a developmental, pubertal and menstrual history should be taken. Some of the symptoms of each of the trophic deficiencies are listed in Table 29.2.
Trophic hormone | History/symptoms | Tests |
---|---|---|
LH/FSH | ||
GH | ||
ACTH | • Insulin tolerance test (often manifestations of complete loss are clear and life threatening, but insufficiency may require an ITT | |
TSH | ||
ADH/vasopressin |
Special tests
Integrated management
Pharmacological
Many of the deficiencies of the hypothalamic-pituitary axis are life threatening. Replacement of glucocorticoids, if these are thought to be deficient, should be done prior to thyroxine replacement and would generally be instigated by an endocrinologist and in hospital. If a patient is in a critical condition, then 200 mg of IV hydrocortisone should be given. Otherwise 100 mg of IV hydrocortisone with 50 mg q6h can be started and blood tests awaited. Maintenance doses of glucocorticoids are not fully elucidated but hydrocortisone equivalent 20–30 mg given in 2–3 divided doses, or cortisone acetate at 25–37.5 mg per day in two divided doses for adults, is a good place to start. The goal is to very slowly and carefully titrate down to the lowest dose that keeps the patient well. Thyroxine may then be replaced if necessary at a dose of 1.6 μg/kg.
PARATHYROID DISORDERS
HYPERCALCAEMIA
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).
Aetiology
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.
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.