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Related Subjects: |Male Infertility |Prolactin |Prolactinoma |Sheehan's syndrome |Acromegaly and Giantism

It is important to measure serum IGF-1 to rule out acromegaly and not to rely on the use of random GH levels

About

• Those with a pituitary tumour causing acromegaly will usually require surgery
• Giantism occurs when GH secretion begins before epiphyses have fused
• Giantism is seen in adolescents. Acromegaly come son usually age 20-40

Aetiology

• Pituitary somatotroph adenomas, usually an 'acidophil' macroadenoma
• Some are due to specific G-protein mutations

Clinical

• Hypertension, Excessive Sweating and offensive body odour
• Enlarged nose, Increased space between teeth
• Spade like hands and thick skin, Hat and Rings don't fit
• Prominent supraorbital ridges with enlarged frontal sinuses
• Prognathism (lower jaw increased growth)
• Enlarged Liver, Heart, tongue, lips, nose, hands
• Carpal tunnel syndrome, feet, heel pad thickness.
• Hyperglycaemia (Type 2 Diabetes Mellitus) and Myopathy.
• Colonic cancer in 5% (age > 50, acromegaly > 10 years and 3 or more skin tags).
• Pituitary Tumour Mass Effects as described above may be seen

Associated conditions

• Sleep apnea syndrome
• Type 2 diabetes mellitus
• Debilitating arthritis
• Carpal tunnel syndrome
• Hyperhidrosis
• Hypertension.

Investigations

• Basic bloods: FBC, U&E, LFT, Glucose, Hba1c: exclude diabetes
• Screening test: Elevated Random IGF-1 x 3-10 times increase. Levels do not fluctuate and this is the first test to do. It is useful to monitor treatment.
• Diagnostic test:Should be taken before breakfast in morning. Usually, it should be less than 5 ng/ml. Transient rises are common. GH varies and so of little use except that undetectable levels rule out Acromegaly. However, usually, it is elevated but that is not diagnostic.
• Check GH with Glucose tolerance test which fails to suppresses GH release: 75 g oral dextrose causing hyperglycaemia should cause a reduction in GH level to < 0.4 mcg/L within 1-2 hours.
• Pituitary MRI with gadolinium : It usually shows a macroadenoma. Visualizes visualize tumour size and appearance, as well as parasellar extent. Adenoma seen in 90% with enlarged sella and thickened skull and prognathism.
• Check LH, FSH, prolactin, free T4, TSH, Testosterone, Estradiol, GH-releasing hormone, Fasting serum glucose, HgA1c
• CT brain with contrast: can be used to image pituitary when MRI is contraindicated
• Formal Perimetry: formal visual field testing is needed when the tumour is found to abut the optic chiasm on an imaging study.
• Prolactin and other Pituitary Hormones :raised in about 30 % of those with acromegaly. Check PRL, TFT, GH, FSH, LH, Cortisol to exclude Hypopituitarism
• Colonoscopy: suggest screening for colon neoplasia with colonoscopy at diagnosis
• BNP, ECG and Echocardiogram : Exclude any causes of heart failure

Differential

• GH-secreting pituitary tumour
• GH/prolactin-secreting pituitary tumour
• GH/GHRH-secreting neuroendocrine tumour (e.g., islet cell tumour of the pancreas)
• Acromegaloidism: acromegalic facies in patient with severe insulin resistance

Management

• Target is the goal of an age-normalized serum IGF-1 value, which signifies control of acromegaly. Also ensuring that a random GH < 1.0 mcg/L as a therapeutic goal, as this correlates with control of acromegaly. Repeat pituitary MRI after 3.6 mo to assess pituitary growth complications and prognosis
• Surgical : Selective trans-sphenoidal surgical resection is the treatment of choice for patients with somatotroph adenomas that are small or large but still resectable. This may need to be repeated. Transfrontal surgery is only used for rare massive tumour s.
• External beam Radiotherapy: to the pituitary tends to be used post-surgery. Can lead to hypopituitary. Also radiation-induced cranial nerve damage, secondary tumour s, radionecrosis, and cognitive changes
• Medical : Combining medical therapies may improve efficacy, reduce side effects associated with an individual medication, decrease the frequency of injections and total drug dose, and, potentially offer a cost-benefit and improved compliance during long-term treatment. Suggest addition of pegvisomant or cabergoline in a patient with inadequate response to an SRL.
• Somatostatin receptor ligand (SRL) may also be involved in the management of disease. Fifty per cent tumour shrinkage has been found in approximately 59% of subjects after SRL administration and correlates with biochemical response. Therefore, primary medical therapy with an SRL may be useful in a patient whose tumour is primary extrasellar, e.g. cavernous sinus, and cannot be removed surgically. Octreotide and lanreotide are analogues of somatostatin and reduce GH secretion and may be used as therapy. There are two equally effective long-acting available preparations: im octreotide long-acting release (LAR), and deep sc lanreotide depot/autogel. These are usually administered monthly.
• Dopamine agonist Cabergoline 0.5 mg daily a dopamine agonist may also be given in addition.
• Growth hormone receptor antagonists :Pegvisomant (10 mg daily) shows good results but is used currently as adjunctive therapy to the other treatments. Helps Symptoms and lower IGF1 in those with acromegaly. It can be used post-surgery to help reduce IGF1 levels.
• Pituitary hormones replacement:

References

• Acromegaly: An Endocrine Society Clinical Practice Guideline
• A Consensus Statement on acromegaly therapeutic outcomes 2018