History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include multiple endocrine neoplasia type 1, familial isolated pituitary adenomas, and Carney complex.

long-standing and progressing symptoms

Most symptoms of pituitary adenomas can be long-standing and slow in progression.

headaches

Headaches can be non-specific.

erectile dysfunction

Symptom of hypogonadism.

soft small testicles

Symptom of hypogonadism.

gynaecomastia

Symptom of hypogonadism.

amenorrhoea

Symptom of hypogonadism.

infertility

Symptom of hypogonadism.

breast atrophy

Symptom of hypogonadism.

loss of libido

Symptom of hypogonadism.

hot flushes

Symptom of hypogonadism.[47]

diaphoresis

Symptom of hypogonadism.[47]

weight gain

Symptom of hypothyroidism.

fatigue

Symptom of hypothyroidism, hypogonadism, and adrenal insufficiency. Reduced energy and vitality can be a symptom of growth hormone deficiency.

anorexia

Symptom of adrenal insufficiency.

nausea

Symptom of adrenal insufficiency.

vomiting

Symptom of adrenal insufficiency.

weakness

Symptom of adrenal insufficiency.

decreased visual acuity

Patients may present with decreased visual acuity before complaining of a visual cut such as bitemporal hemianopia.

bitemporal hemianopia

A superior temporal quadrantanopia with red desaturation (dimmer perception of the colour red) is usually the earliest clinical feature of chiasmal pressure.

uncommon

pituitary apoplexy

Acute onset of severe headache, associated with nausea, vomiting, meningismus, altered level of consciousness, ophthalmoplegia, hypotension in acute adrenal crisis.

diplopia

Diplopia and facial numbness secondary to cranial nerve palsies affecting the third, fourth, fifth (V1 and V2), and sixth nerves.

Other diagnostic factors

common

increased central adiposity

Sign of growth hormone deficiency and hypogonadism.

reduced muscle mass

Symptom of hypogonadism in men, and of growth hormone deficiency in men and women.

constipation

Symptom of hypothyroidism.

cold intolerance

Symptom of hypothyroidism.

dry skin

Symptom of hypothyroidism.

hair loss

Symptom of hypothyroidism.

poor memory

Symptom of hypothyroidism, growth hormone deficiency, and hypothalamic extension of the tumour.

low mood

Symptom of hypothyroidism and hypogonadism.

osteopenia

Associated with hypogonadism or growth hormone deficiency.

uncommon

weight loss

Symptom of adrenal insufficiency.

nervousness

Symptom of adrenal insufficiency; not typical but has been reported to be found more frequently in patients with adrenal insufficiency.[48]

facial numbness

Diplopia and facial numbness secondary to cranial nerve palsies affecting the third, fourth, fifth (V1 and V2), and sixth nerves.

imbalance

Associated with tumour growth in the third ventricle resulting in hydrocephalus or can be associated with postural hypotension from secondary adrenal insufficiency.

urinary incontinence

Associated with tumour growth in the third ventricle or secondary to diabetes insipidus.

recurrent sinusitis

May result from growth in the sphenoid sinus.

bradycardia

Sign of hypothyroidism.

seizures

May occur secondary to metabolic dysfunction (such as hyponatraemia and hypoglycaemia) resulting from adrenal insufficiency or from temporal lobe involvement.

Risk factors

strong

multiple endocrine neoplasia type 1 (MEN-1)

Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant condition associated with pituitary adenomas in 40% to 60% of patients. There is a germline mutation in MEN-1 gene on chromosome 11q13. The MEN-1 gene product is menin, which is a regulatory protein and interacts with a broad range of targets. MEN-1 may be associated with non-functional or functional pituitary tumours, among which prolactinoma is the most common. In about 10% of patients with MEN-1, no gene mutation is identified. Female sex is associated with increased risk of having a pituitary tumour. Pituitary adenomas in MEN-1 are mostly macro-adenomas at presentation and tend to be more aggressive.[31]

familial isolated pituitary adenomas (FIPA)

Familial pituitary adenomas in the absence of MEN-1 and Carney complex are rare. However, a retrospective study of clinical characteristics of familial isolated pituitary adenomas at 22 centres across western Europe yielded 64 such kindreds, with 138 affected individuals. A first-degree relative is involved in about 75% of cases. Patients usually present at a younger age than sporadic cases and about 20% have non-functional pituitary adenomas.[32] Inactivating mutations involving the aryl hydrocarbon receptor interacting protein (AIP) gene have been described in FIPA.

Carney complex (CNC)

CNC is a rare familial condition characterised by lentigines, myxomas, Schwan cell tumours, adrenal hyperplasia, and pituitary abnormalities. CNC is associated with mutations in the protein kinase A 1-alpha regulatory subunit (PRKAR1A) gene in 60% of cases. Pituitary disease is characterised by hypersecretion of prolactin and growth hormone. Pituitary tumours occur in about 20% of cases and tend to exhibit somatomammotropin cell multifocal hyperplasia.[33]​​

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