Pituitary Disorders — Symptoms, Causes & Treatment | MyMedicPlus

The pituitary gland is a pea-sized structure situated at the base of the brain in the sella turcica — a bony depression in the sphenoid bone — directly below the hypothalamus and immediately above the optic chiasm. Despite its small size (0.5g, approximately 10x6x8mm), it is the 'master gland' of the endocrine system: the anterior pituitary (adenohypophysis) secretes six tropic hormones — growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), follicle-stimulating hormone (FSH), luteinising hormone (LH), and prolactin — each regulated by hypothalamic releasing and inhibiting hormones; the posterior pituitary (neurohypophysis) stores and releases antidiuretic hormone (ADH/vasopressin) and oxytocin from the hypothalamus. Pituitary disorders encompass a broad spectrum: hormone-secreting (functioning) pituitary adenomas — of which prolactinoma is the most common (40-50% of all pituitary adenomas), followed by GH-secreting adenomas (causing acromegaly — insidious onset over 8-10 years before diagnosis) and ACTH-secreting adenomas (causing Cushing's disease); non-functioning pituitary adenomas (null cell, gonadotroph adenomas — causing mass effects including headache and visual field loss without hormone excess); and hypopituitarism — deficiency of one or more pituitary hormones from any cause. Pituitary adenomas are extremely common incidental findings (estimated 10% of the population on MRI — 'pituitary incidentaloma') but clinically significant disease requiring treatment affects approximately 1 in 1,000 people.

Pituitary adenomas arise from clonal expansion of a single pituitary cell type — driven by somatic mutations in cell cycle regulatory genes (AIP — aryl hydrocarbon receptor-interacting protein — mutation in 15-20% of young-onset acromegaly; GNAS — in 30-40% of GH-secreting adenomas causing constitutive Gs-alpha activation). Most pituitary adenomas are sporadic, but genetic syndromes account for up to 5%: multiple endocrine neoplasia type 1 (MEN1 — MEN1 gene mutation — predisposing to pituitary adenomas in 40%, plus parathyroid adenoma in 90%, and pancreatic neuroendocrine tumours); Carney complex (PRKAR1A mutation — GH-secreting adenomas plus cardiac myxomas, skin lesions); familial isolated pituitary adenoma (FIPA — AIP or GPR101 mutations — typically GH-secreting, young onset). Causes of hypopituitarism: pituitary macroadenoma compressing normal gland tissue (most common cause); pituitary surgery (transsphenoidal surgery — up to 30% develop new anterior pituitary deficiency); pituitary radiotherapy (delayed, progressive hypopituitarism over years); head trauma (traumatic brain injury causing hypothalamic-pituitary axis disruption — underrecognised cause); Sheehan's syndrome (postpartum pituitary necrosis from haemorrhagic shock during childbirth — causing panhypopituitarism); pituitary apoplexy (sudden haemorrhage or infarction within a pre-existing adenoma — acute pituitary crisis); infiltrative diseases (sarcoidosis, lymphocytic hypophysitis — often peripartum in women, causing mass effect on stalk and posterior pituitary deficit, diabetes insipidus); craniopharyngioma (embryonic remnant tumour in children and young adults — causes hypothalamic-pituitary dysfunction, visual impairment, and is notoriously difficult to treat).

Symptoms arise from three mechanisms: mass effect from adenoma enlargement; hormone excess from functioning adenomas; and hormone deficiency from compression or destruction of normal pituitary tissue. Mass effect: headache (retro-orbital or bifrontal, from dural stretch by the enlarging adenoma — not well correlated with tumour size); bitemporal hemianopia (loss of the outer half of each visual field from chiasmal compression by a macroadenoma extending superiorly — detected on formal Humphrey perimetry); cranial nerve III, IV, VI palsies from lateral cavernous sinus invasion (ptosis, diplopia). Prolactinoma (most common secreting adenoma): galactorrhoea (nipple discharge in 80% of women; 30% of men); amenorrhoea or oligomenorrhoea; infertility from anovulation; sexual dysfunction, gynaecomastia, and azoospermia in men — serum prolactin typically above 5000 mU/L (microadenoma) or above 50,000 mU/L (macroadenoma). Acromegaly (GH/IGF-1 excess): progressive acral enlargement (hands — ring size increase, feet — shoe size increase), coarsening of facial features, jaw prognathism (protrusion), macroglossia, soft tissue swelling, hyperhidrosis, oily skin, hypertension, type 2 diabetes, OSA, arthropathy, carpal tunnel syndrome, and colonic polyps (requiring colonoscopic surveillance). Cushing's disease (ACTH excess → bilateral adrenal cortisol excess): centripetal obesity (central fat deposition with limb wasting), moon face, buffalo hump, violaceous striae (purple stretch marks wider than 1cm on abdomen), proximal muscle weakness, thin skin, easy bruising, hypertension, T2DM, osteoporosis (vertebral fragility fractures), depression, and severe immune suppression causing opportunistic infections. Hypopituitarism: fatigue, cold intolerance, weight gain (secondary hypothyroidism); pallor, hypotension (secondary adrenal insufficiency — may present as adrenal crisis); sexual dysfunction, amenorrhoea, infertility (gonadotropin deficiency).

MRI pituitary gland with dynamic gadolinium contrast is the gold standard imaging investigation: superior soft tissue resolution distinguishes microadenoma (below 10mm — appears as hypointense lesion relative to enhancing normal pituitary on dynamic post-contrast sequences) from macroadenoma (10mm and above), and assesses optic chiasm position and compression, cavernous sinus invasion, and suprasellar/sphenoid extension. CT skull base is used when MRI is contraindicated or for surgical planning. Formal visual field assessment (Humphrey automated perimetry) is mandatory for all patients with pituitary macroadenomas abutting or compressing the optic chiasm — a baseline for surgical outcome monitoring. Hormonal workup: serum prolactin (stalk effect from any pituitary or hypothalamic mass raises prolactin moderately to 1000-5000 mU/L without a true prolactinoma — 'hook effect' at very high prolactin levels requires sample dilution); IGF-1 (acromegaly screening — elevated in 97% of acromegaly); oral glucose tolerance test with GH measurement (GH fails to suppress below 0.4 ng/mL confirming acromegaly); 24-hour urinary free cortisol (UFC) or late-night salivary cortisol (Cushing's — both above upper limit of normal on 2 occasions confirms hypercortisolism); 1mg overnight dexamethasone suppression test (cortisol above 50 nmol/L confirms excess); 9am cortisol and short Synacthen test (ACTH stimulation test — diagnoses secondary adrenal insufficiency in hypopituitarism; cortisol below 300 nmol/L at baseline is suspicious); LH, FSH, testosterone or oestrogen, free T4 and TSH (assess all pituitary axes). Inferior petrosal sinus sampling (IPSS): bilateral simultaneous IPSS with CRH stimulation is the gold standard for distinguishing pituitary Cushing's disease from ectopic ACTH secretion when imaging is inconclusive.

Treatment is tailored to adenoma type, size, and hormonal activity. Prolactinoma: dopamine agonists are first-line for all prolactinomas regardless of size — cabergoline (0.5-2mg twice weekly) normalises prolactin in 85-90%, shrinks tumour in 70-80% of macroadenomas (often dramatically), and restores fertility; preferred over bromocriptine for tolerability and efficacy; macroprolactinomas may require 6-24 months of cabergoline before significant size reduction; surgery (TSS) reserved for dopamine agonist resistance or intolerance, or acute chiasmal compression. Acromegaly: transsphenoidal surgery (TSS) — the primary treatment for most GH-secreting microadenomas and accessible macroadenomas; surgical remission achieved in 80-90% of microadenomas and 40-60% of macroadenomas; somatostatin receptor analogues (SRLs: octreotide long-acting release 10-40mg IM monthly, lanreotide autogel 60-120mg SC monthly) suppress GH/IGF-1 in 55-70% and are first-line for patients not cured by surgery or unsuitable for surgery; pasireotide (second-generation SRL) for SRL-refractory acromegaly; pegvisomant (GH receptor antagonist, 10-30mg SC daily) — normalises IGF-1 in 90%, used for SRL-refractory cases or adjunct therapy; Gamma Knife radiosurgery (SRS) for residual post-operative disease achieves remission in 40-60% at 5 years but risks delayed hypopituitarism. Cushing's disease: TSS is first-line — remission in 60-85% for experienced pituitary surgeons; medical therapy for recurrent or persistent disease: osilodrostat (11-beta-hydroxylase inhibitor, rapidly effective), metyrapone, ketoconazole, pasireotide; bilateral adrenalectomy as rescue therapy. Hypopituitarism hormone replacement: hydrocortisone 15-25mg/day in divided doses (ACTH deficiency — must replace cortisol before thyroid hormone to prevent precipitating adrenal crisis); levothyroxine (TSH deficiency — dosed by free T4, not TSH); sex hormone replacement (testosterone gel/injections for men, oestrogen-progesterone for premenopausal women); GH replacement in adults (0.2-0.4mg SC daily) improves body composition, quality of life, and cardiovascular risk markers; desmopressin (DDAVP) for ADH deficiency.

Pituitary apoplexy: sudden haemorrhage or infarction within a pituitary adenoma — presenting as acute thunderclap headache, vomiting, visual disturbance (bitemporal hemianopia, cranial nerve III/IV/VI palsies causing diplopia), and acute cortisol deficiency (haemodynamic compromise, loss of consciousness) — neurosurgical emergency requiring urgent MRI, immediate IV hydrocortisone 100mg (before waiting for cortisol result), and surgical decompression within 1 week for visual compromise. Visual field loss: bitemporal hemianopia from chiasmal compression by macroadenomas may become permanent if surgical decompression is substantially delayed (above 2-3 weeks); perimetry monitoring is mandatory for all non-functioning macroadenomas managed conservatively. Adrenal crisis: the most immediately life-threatening complication of hypopituitarism — caused by ACTH deficiency resulting in cortisol insufficiency during physiological stress; presents with hypotension, hypoglycaemia, vomiting, and collapse; requires immediate IV or IM hydrocortisone 100mg and emergency hospitalisation. Cushing's disease complications: premature atherosclerosis (2-5x cardiovascular mortality), severe muscle wasting (proximal myopathy), osteoporotic vertebral fractures (occurring in 70-80% if untreated), immune suppression with opportunistic infections (PCP, invasive fungal), glucose intolerance, and severe depression with suicide risk. Acromegaly: untreated or late-diagnosed GH excess causes irreversible left ventricular hypertrophy (4-5x cardiac mortality), colon polyps (3-fold increased colon cancer risk), sleep apnoea (70%), arthritis (irreversible cartilage loss), and 2-3x overall mortality reduction achievable with normalisation of GH/IGF-1. Hypopituitarism: untreated GH deficiency causes central obesity, dyslipidaemia, reduced muscle mass and bone density, impaired quality of life, and cardiovascular mortality.

Pituitary adenomas cannot be prevented in the general population. The key preventive goals are early diagnosis before complications (visual loss, cardiovascular disease from acromegaly or Cushing's, adrenal crisis from undiagnosed hypopituitarism) and systematic long-term monitoring to detect tumour recurrence or progression and ensure adequate hormone replacement. Annual surveillance pituitary MRI (reducing frequency to 2-3 yearly once stability confirmed) for non-functioning microadenomas not meeting surgical criteria — surgery indicated if growth above 3-4mm or approach to the optic chiasm. Hormone replacement monitoring: annual free T4, 9am cortisol (or annual clinical reassessment of sick-day rule adherence), LH/FSH/testosterone or oestradiol, IGF-1; avoid under-dosing hydrocortisone (inadequate cortisol replacement causes fatigue, weight loss, hypoglycaemia) or over-dosing (Cushing's features, osteoporosis, metabolic syndrome — daily hydrocortisone above 25mg/day substantially worsens outcomes). Patient education on the sick-day rule: patients with ACTH deficiency must double or triple their hydrocortisone dose during any intercurrent illness, surgery, or significant physiological stress — carry a steroid emergency identification card, MedicAlert bracelet, and pre-filled IM hydrocortisone 100mg syringe for inability to take oral medication. Genetic counselling and cascade testing with MEN1 gene testing for all first-degree relatives of a patient with confirmed MEN1 syndrome. Acromegaly surveillance for comorbidities: annual colonoscopy from diagnosis (colonic polyp risk), cardiovascular monitoring, sleep study for OSA.

Call emergency services (999/112) or go to A&E immediately for suspected pituitary apoplexy: sudden thunderclap or severe 'worst headache of life'; combined with rapid visual loss or double vision (optic chiasm or cranial nerve compression); and altered consciousness or severe drowsiness. Pituitary apoplexy is a neurosurgical emergency — delay in steroid replacement and surgical decompression risks permanent visual loss and pituitary failure. Go to A&E for adrenal crisis in a known hypopituitary patient: collapse, severe vomiting, inability to take oral medications, severe infection with hypopituitarism — administer IM hydrocortisone 100mg immediately and call 999. See an endocrinologist urgently for: progressive visual field loss from a pituitary macroadenoma — any bitemporal hemianopia (loss of outer visual fields) requires urgent MRI and surgical assessment; rapidly growing prolactinoma symptoms (galactorrhoea, amenorrhoea, severe headache); symptoms of acromegaly (hand and foot enlargement, facial changes over years) or Cushing's disease (weight gain with striae, muscle weakness, easy bruising). All patients with hypopituitarism should carry a steroid emergency card and know how to self-administer IM or IM hydrocortisone for emergency sick-day rules.