How not to miss – acromegaly

Acromegaly is most commonly caused by growth hormone (GH)-secreting tumours of the pituitary gland.  

Worst outcomes if missed

• Pituitary macroadenomas - the worst outcomes are typically seen in young patients. Most patients present with pituitary macroadenomas (tumours >1cm) and those invading the cavernous sinus or bone which are unable to be fully resected surgically. These patients may also require medical therapy - somatostatin analogue therapy with or without dopamine agonists.
• Loss of visual field - the macroadenomas also cause visual field defects and ophthalmoplegia, which if left undiagnosed may become permanent.
• Death - patients with acromegaly have a 32% increased risk for all-cause mortality.¹ The tumours themselves are almost always benign but the elevated growth hormone and insulin-like growth factor-1 (IGF-1) levels result in a range of morbidities, including impaired glucose tolerance, type 2 diabetes mellitus, left ventricular hypertrophy, hypertension, cardiac failure, thyroid nodules, and colonic polyps. 

Epidemiology

Acromegaly has an incidence of four cases per million of the UK population per year. Most GPs will encounter one case of acromegaly in their career. The vast majority of tumours are sporadic but they can also be associated with the rare genetic conditions of multiple endocrine neoplasia type 1 (MEN1), familial isolated pituitary adenoma (FIPA) and McCune-Albright syndrome.  

Symptoms and signs

Symptoms and signs can relate to the effects of the excess GH, the pressure effect of the tumour itself or due to hypopituitarism:

Effects of growth hormone excess

• Increased growth of extremities
• Prominent supraorbital ridge
• Prognathism
• Increased interdental spacing
• Sweating
• Headache
• Macroglossia
• Sleep apnoea
• Left ventricular hypertrophy
• Hypertension
• Colonic polyps progressing to cancer
• Impaired glucose tolerance and type 2 diabetes

Mass effect from the pituitary tumour itself

• Bitemporal hemianopia due to compression of the optic chiasm
• Opthalmoplegia due to involvement of cranial nerves III, IV and VI if the tumour invades the cavernous sinus
• CSF rhinorrhoea if there is bone invasion

Symptoms and signs related to hypopituitarism

• Lethargy, low mood, weight gain, cold intolerance (due to secondary hypothyroidism)
• Low libido, loss of body hair (males), oligo- or amenorrhoea, subfertility (due to hypogonadism)
• Postural hypotension, collapse (due to adrenocorticotropic hormone deficiency)

Differential diagnosis

Patients can go undiagnosed for up to 10 years. Care must be taken when eliciting the history to piece together all the individual symptoms and signs to make the over-arching diagnosis of acromegaly.

Patients most commonly present with headache, excessive sweating and an increase in the size of their hands and feet.  Patients can easily be diagnosed with, for example, sleep apnoea or type 2 diabetes mellitus alone for many years prior to the diagnosis of acromegaly being made, as physicians were not considering this in their differential. These diagnoses occurring in combination with the symptoms mentioned above should make you consider acromegaly.   

Prolactinomas are the most common functioning pituitary tumour and 10% of them co-secrete GH. Always check a prolactin level in patients presenting with features suggestive of acromegaly in combination with hypogonadism or galactorrhoea as prolactinomas respond very well to dopamine agonist therapy.

Endocrine disorders that can mimic acromegaly by causing hypertension and sweating include Cushing’s syndrome - which also causes impaired glucose tolerance - thyrotoxicosis and phaeochromocytoma.

Investigations

Blood tests include an insulin-like growth factor-1 level which, if elevated, should prompt referral to the endocrinology department for further investigation. An oral glucose tolerance test to assess for failure of suppression of GH will then be performed by the specialist centre to confirm the diagnosis biochemically. Random GH levels are variable and should not be requested as they are not useful unless very high.  

Fasting serum glucose and lipid profile should also be measured along with blood pressure and treatment initiated in primary care if abnormal.

To assess baseline pituitary function the specialist centre will arrange the following:

• 9am cortisol
• Prolactin
• TSH
• Free T4
• Luteinising hormone (LH)
• Follicle stimulating hormone (FSH)
• Testosterone/oestradiol.    

MRI of the pituitary with gadolinium enhancement is the imaging modality of choice to identify the tumour and examine the extent of tumour spread beyond the pituitary fossa. Formal visual field testing is performed to accurately assess the extent of any defect. If your patient has a visual field defect, you should refer the patient promptly.

All patients will undergo a baseline colonoscopy and echocardiogram due to the increased risk of colon cancer and heart disease.

Dr Angela Rogers is a Wellcome Trust Clinical Training Fellow at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford and Professor John Wass is a professor of endocrinology in the Department of Endocrinology at OCDEM.

It is estimated that there are between 50,000 and 70,000 pituitary patients in the United Kingdom. To meet the need for information and support, in 1994, The Pituitary Foundation was launched, with charitable status following in September 1996. The Foundation is now a national support and information organisation for pituitary patients, their families, friends and carers. The Foundation operates throughout the UK and Republic of Ireland. Our website and National Support Helpline 0845 450 0375

References

1. Melmed S, Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, Clemmons D, Chanson P, Laws E, Schlechte J, Vance ML, Ho K, Giustina A,. (2009) Guidelines for acromegaly management: an update. Journal of Clinical Endocrinology and Metabolism, 94 (5): 1509-1517.