42. Anterior lobe pituitary tumours and their consequences. Posterior lobe syndromes. Disorders associated with hypopituarism (Sheehan syndrome, chromophobic adenoma, empty sella syndrome, suprasellar tumours)

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Anterior lobe pituitary tumours

Pituitary adenomas or pituitary neuroendocrine tumours arise in the anterior lobe of the pituitary. This lobe is normally comprised of many different cell types, each of which produce different hormones. These cells are:

  • Chromophobe cells
  • Chromophile cells
    • Acidophilic cells
      • Somatotrophs – produce growth hormone
      • Lactotrophs – produce prolactin
    • Basophilic cells
      • Corticotrophs – produce ACTH
      • Thyrotrophs – produce TSH
      • Gonadotrophs – produce FSH, LH

As one might expect, anterior lobe pituitary tumors may produce pituitary hormones. These tumors are most commonly sporadic, but some cases are associated with multiple endocrine neoplasia type 1.

These tumors are classified according to three different parameters: whether they produce hormones or not, and if they do, which hormones they produce, and whether they are larger or smaller than 1 cm in diameter. Tumors that produce hormones are functional or secretory, while those that don’t are non-functional, non-secretory or chromophobe adenomas. Tumors that are larger than 1 cm in diameter are macroadenomas while those that are smaller than 1 cm are microadenomas. Most pituitary adenomas are non-functional.

The functional tumors can be further classified according to the hormone they produce, in order from most common to least common:

Tumor type Originating cell Hormone produced Associated syndrome or symptoms
Prolactinoma / prolactin cell adenoma Lactotroph cells Prolactin Galactorrhoea, amenorrhoea, sexual dysfunction, infertility
Somatotroph adenoma / growth hormone cell adenoma Somatotroph cells Growth hormone Gigantism in children, acromegaly in adults
Corticotroph adenoma Corticotroph cells ACTH Cushing disease
Thyrotroph adenoma Thyrotroph cells TSH Secondary hyperthyroidism
Gonadotroph adenoma Gonadotroph cells FSH, LH Hypogonadism

Plurihormonal adenomas (which produce more than one hormone) and pituitary carcinomas are very rare.

Mutations in the gene GNAS1 is common in pituitary tumors. This gene codes for a stimulatory G protein (Gs). When this gene is mutated the Gs protein will be constitutively active, continuously stimulating adenylyl cyclase and causing the cells to proliferate uncontrollably.

Consequences

The most common cause of hyperpituitarism (increased level of one or more pituitary hormones) is a functional anterior lobe pituitary adenoma. The exact symptom of an anterior pituitary adenoma depends on which hormone it produces.

While functional pituitary adenomas cause hyperpituitarism, non-functional pituitary adenomas cause hypopituitarism. This is because the non-hormone secreting tumors produce fewer symptoms, which allows them to grow larger before they’re treated, becoming macroadenomas. As they grow, they will obliterate the rest of the pituitary, eventually causing panhypopituitarism (see below).

Non-functional pituitary macroadenomas may also cause increased intracranial pressure and visual defects as they press on the optic chiasm. Non-functional microadenomas are usually asymptomatic and are not treated.

Posterior pituitary syndromes

The posterior pituitary itself doesn’t produce any hormones; it just secretes them. It consists of axonal processes extending from nerve cell bodies in the hypothalamus, where the hormones are produced. Two hormones are secreted from the hypothalamus: antidiuretic hormone (ADH) and oxytocin. The clinically relevant posterior pituitary syndromes involve abnormalities of ADH production, either too much or too little.

ADH deficiency causes central diabetes insipidus, as the renal tubules lose their ability to reabsorb free water, resulting in polyuria and polydipsia. The most common causes of central diabetes insipidus are:

  • Idiopathic
  • Brain tumors – compressing the posterior pituitary
  • Traumatic brain injury – causing haemorrhage of the pituitary

Syndrome of inappropriate ADH secretion (SIADH) is exactly what the name says. It’s caused by excessive production of ADH. It’s usually caused by ADH-producing tumors, especially small cell lung cancer, as a paraneoplastic syndrome. Symptoms include normovolaemic hyponatraemia and cerebral oedema. See pathophys 1 for more details.

Hypopituitarism

Hypopituitarism refers to the inadequate production of one or more anterior pituitary hormones. It occurs due to damage to the pituitary or less frequently, the hypothalamus. If secretion of both anterior and posterior pituitary hormones is affected the condition is called panhypopituitarism.

The most important causes are:

  • Non-functional pituitary macroadenomas – most common cause
  • Pituitary apoplexy
    • Sheehan syndrome
    • Traumatic brain injury
  • Infiltration of the pituitary or hypothalamus
    • Haemochromatosis
    • Meningitis
    • Tuberculosis

The symptoms depend on which hormones are affected. An interesting point is that in hypopituitarism, the different pituitary hormones are lost in a special sequence. When the pituitary is damaged the hormones are lost in the following order:

GH -> FSH and LH -> TSH -> ACTH -> prolactin

Because of this, the first symptom is often that of GH deficiency, which causes dwarfism in children but is mostly asymptomatic in adults. This occurs only if the pituitary is damaged over time; if the damage is sudden all pituitary hormones will be deficient.

Sheehan syndrome is a special case. It’s caused by ischaemic necrosis of the pituitary due to blood loss during or after childbirth. The first symptom is often that the mother can’t lactate, due to the prolactin deficiency.

Empty sella syndrome is the condition where the pituitary gland is shrunk or flattened, which causes the sella turcica to be filled with CSF instead. It may occur primarily due to idiopathic causes, or secondarily to pituitary apoplexy or surgical removal of the pituitary. Only a small number of people with empty sella syndrome actually have hypopituitarism, and the syndrome rarely causes any symptoms on its own. It’s usually an incidental finding on CT or MRI of the brain.

Suprasellar tumors are tumors that are above the sella turcica, in the suprasellar cistern. The infundibulum lies in this cistern, so tumors in this area may affect the function of the pituitary, causing hypopituitarism or panhypopituitarism. The following tumors may occur suprasellarly:

  • Craniopharyngioma
  • Glioma
  • Lipoma
  • Rathke’s cyst