What are the typical symptoms and clinical presentations of pituitary adenomas?

Pituitary Adenoma Symptoms

Hormone Hypersecretion Syndromes

Pituitary adenomas present with distinct clinical patterns depending on which hormone is overproduced, with prolactinomas being the most common functioning tumor type, accounting for 53% of all pituitary adenomas. 1

Prolactinoma Manifestations

• In females: delayed or arrested puberty, primary amenorrhea, secondary amenorrhea, menstrual disturbances, galactorrhea, infertility, and growth failure 2, 3
• In males: hypogonadism, decreased libido, erectile dysfunction, gynaecomastia, and infertility 3, 4
• In children and adolescents: growth arrest, delayed puberty (>2 standard deviations later than mean population age), and short stature are particularly prominent 2
• Median symptom duration before diagnosis is 12 months, and 46% of pediatric patients with macroprolactinomas present with overweight or obesity 2

Growth Hormone Excess (Acromegaly/Gigantism)

• Enlargement of lips, tongue, nose, hands, and feet in adults (acromegaly) 4
• Excessive linear growth in children and adolescents before epiphyseal closure (gigantism) 2
• Glucose intolerance and hypertension as metabolic complications 2
• Co-secretion of prolactin occurs in 65% of cases, and hyperprolactinaemia is present in 34-36% of pediatric gigantism cases 2

ACTH-Secreting Tumors (Cushing Disease)

• Obesity, hypertension, diabetes mellitus, and characteristic cushingoid features 4, 1
• These tumors account for 4% of pituitary adenomas 1

TSH-Secreting Tumors (Thyrotropinomas)

• Hyperthyroidism symptoms, though these are rare, accounting for only 1% of pituitary adenomas 3, 4

Mass Effect Symptoms

Macroadenomas (≥10 mm) commonly produce symptoms through compression of adjacent structures, with headache being the most frequent presenting complaint. 5

Neurological Manifestations

• Headache occurs in 17-75% of patients with macroadenomas 1, 5
• Visual disturbances affect 18-78% of patients, including bitemporal hemianopsia, visual field defects, and loss of central visual acuity due to optic chiasm compression 3, 1, 5
• Cranial nerve palsies (III, IV, VI) cause diplopia and ocular motility problems in large tumors extending into the cavernous sinus 3, 6
• Raised intracranial pressure can develop in severe cases 6, 5
• The classic triad of headache, visual impairment, and hypogonadism represents the most common presenting constellation in surgical series 6, 5

Pituitary Apoplexy

• Acute hemorrhage or infarction presents with sudden severe headache, visual loss, and altered consciousness 6, 5
• This occurs in approximately 29% of invasive macroadenomas and represents a neurosurgical emergency 5

Hypopituitarism

Hypopituitarism occurs in 34-89% of patients with macroadenomas due to compression of normal pituitary tissue, causing deficiency of one or multiple pituitary hormones. 1, 5

Specific Hormone Deficiencies

• Growth hormone deficiency: growth failure, short stature in children 3
• Gonadotropin deficiency: delayed or arrested puberty, hypogonadism 3
• TSH deficiency: hypothyroidism with fatigue, cold intolerance, weight gain 3
• ACTH deficiency: hypocortisolism causing fatigue, weakness, hypotension 3
• Central diabetes insipidus is extremely rare at initial presentation unless pituitary apoplexy has occurred 6, 5

Age and Sex-Specific Presentations

Pituitary adenomas are 3-4.5 times more common in females than males, though this sex predisposition is most pronounced for prolactinomas. 2, 3, 5

Pediatric and Adolescent Features

• Children and adolescents are more likely to have functioning tumors, particularly macroprolactinomas or giant prolactinomas 2, 3
• Disease behavior is more aggressive in young patients compared to adults 2, 5
• 93% of pediatric prolactinomas present after 12 years of age, though they can occur in the first decade 2
• Pituitary adenomas can disrupt maturational, visual, intellectual, and developmental processes in children 3
• A Ki-67 labeling index ≥3% combined with radiologic invasion predicts 25% recurrence rate after surgery in young patients 6

Adult Presentations

• Females tend to present at an earlier disease stage, often prompted by menstrual abnormalities 3
• Males more commonly present with mass effects than females 2

Non-Functioning Pituitary Adenomas

Non-functioning adenomas account for 30% of all pituitary adenomas and typically present with mass effects rather than hormonal syndromes. 1

Clinical Characteristics

• Microadenomas (<10 mm) are usually asymptomatic and discovered incidentally on imaging (pituitary incidentalomas) 3, 5
• Macroadenomas present with headache, visual field defects, and hypopituitarism 3, 5
• Non-functioning adenomas represent 4-6% of pediatric cases but 15-30% of adult cases, accounting for 50-60% of surgical series in adults 5

Critical Clinical Considerations

Visual assessment with formal visual field testing is mandatory for any suspected pituitary macroadenoma, as visual deterioration represents an urgent indication for surgical decompression. 3, 5

Diagnostic Pitfalls

• Macroprolactin should be checked in mildly elevated prolactin cases, as macroprolactinaemia occurs in 10-40% of adults with hyperprolactinaemia and has low biological activity 3, 5
• High-dose hook effect: Large pituitary lesions may show paradoxically normal or mildly elevated prolactin due to immunoassay saturation; serial dilutions are required 3, 5
• Stalk effect: Macroadenomas may cause mild hyperprolactinaemia (typically <2,000 mU/L) due to stalk compression, which should not be confused with a prolactinoma 6

Genetic Screening

• Genetic testing should be considered in all patients with pituitary adenomas, particularly children and young adults, due to higher likelihood of familial isolated pituitary adenoma, MEN1, MEN1-like syndromes, or AIP gene mutations 2, 3, 5

Timing and Urgency

• Early diagnosis is crucial, as pituitary adenomas can cause irreversible visual loss and developmental disruption in children 3
• Visual field recovery is unlikely after the first post-operative month, emphasizing the need for prompt intervention when vision is threatened 5