History and exam
Key diagnostic factors
common
coarsening of facial features
Changes can include frontal bossing, enlarged nose, jaw enlargement, prognathism and separation of teeth, and macroglossia.
Patients and close contacts are usually unaware of early physical changes. Progressive morphological changes due to growth hormone/insulin-like growth factor 1 excess eventually become evident in all patients.[Figure caption and citation for the preceding image starts]: Patient with typical features of acromegalyFrom the collection of Dr Omar Serri; used with patient permission [Citation ends].
soft-tissue and skin changes
Changes can include increased skin thickness and soft-tissue hypertrophy, skin tags, and increased sweating.
Soft-tissue hypertrophy is usually due to intradermal accumulation of glycosaminoglycans secondary to growth hormone/insulin-like growth factor 1 actions.
carpal tunnel syndrome
Carpal tunnel syndrome, often bilaterally, may be an early manifestation of the disease.
Growth hormone/insulin-like growth factor 1-mediated soft-tissue hypertrophy causes the condition. Generally, it is reversible with acromegaly control.
joint pain and dysfunction
Arthropathy is a complication of a long-standing disease.
Growth hormone/insulin-like growth factor 1-mediated overgrowth of cartilage is the operative mechanism. Often progresses independently of acromegaly control with osteoarthritis developing in affected joints.
snoring
Sleep apnoea can occur due to upper airway obstruction-macroglossia and soft-tissue swelling secondary to growth hormone/insulin-like growth factor 1 excess.
alterations in sexual functioning
Changes can include reduced libido, infertility, amenorrhoea/oligomenorrhoea, galactorrhoea, and erectile dysfunction.
These symptoms are due to the effects of hyperprolactinaemia resulting from prolactin co-secretion by the adenoma or pituitary stalk compression (30% to 40% of cases).[5] They may also result from gonadotrophin deficiency secondary to tumour mass.
uncommon
history or family history of inherited syndrome
Acromegaly can be present in association with multiple endocrine neoplasia type 1 syndrome (seen in 14% of patients), McCune-Albright syndrome (rarely), and Carney complex (rarely), and may present as an isolated familial condition (extremely rare condition, with <200 affected families worldwide).
Other diagnostic factors
common
fatigue
Multi-factorial in origin.
hypertension, arrhythmias
These findings may be associated with hypertrophic cardiomyopathy.
Excessive levels of growth hormone/insulin-like growth factor 1 can cause major structural and functional cardiac changes that are associated with increased morbidity and premature mortality.
organomegaly
Goitre or prostate enlargement may be present.
Growth hormone/insulin-like growth factor 1 overproduction has a trophic effect on major organs.
increased appetite, polyuria/polydipsia
Impaired glucose tolerance or diabetes mellitus may be present.
These occur as a result of insulin resistance due to chronic growth hormone excess.
headaches
May be related or unrelated to tumour mass effect. About 50% of acromegaly patients report headaches.
uncommon
visual field defects
Due to optic compression by tumour mass.
signs and symptoms of hypopituitarism
Caused by pituitary stalk compression; vary widely, depending on which hormones are deficient; key diagnostic factors may include infertility, amenorrhoea/oligomenorrhoea, delayed puberty due to gonadotrophin deficiency, and hypoglycaemia and hypotension due to adrenal insufficiency.
cranial nerve palsies (e.g., ophthalmoplegia)
Due to parasellar tumour mass extension.
Risk factors
weak
GPR101 over-expression
In one study, patients with early-onset acrogigantism (<5 years old) were found to have microduplication on chromosome Xq26.3 with over-expression of GPR101, a gene that encodes an orphan G-protein-coupled receptor.[10] GPR101 was over-expressed in patients' pituitary lesions.
multiple endocrine neoplasia type 1 syndrome
Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal-dominant syndrome characterised by pituitary adenomas in 10% to 40% of cases. This includes somatotroph adenomas (in up to 14% of cases), primary hyperparathyroidism, and pancreatic neuroendocrine tumours, due to germline mutations in the gene encoding menin (MEN-1) located on chromosome 11q13.[6]
isolated familial acromegaly
Isolated familial acromegaly is defined as the occurrence of at least two cases of acromegaly or gigantism in a family that does not exhibit features of Carney complex or MEN-1. This condition has been reported in <200 families worldwide. Loss of heterozygosity at chromosome 11q13 has been reported in both sporadic (20% to 40%) and familial (>90%) somatotroph adenomas.[6]
Inactivating germline mutations of the gene encoding aryl hydrocarbon receptor-interacting protein (AIP) have been identified in about 15% of familial pituitary adenomas with predominant expression of growth hormone (GH) and/or prolactin-secreting tumours. This gene is located on chromosome 11q13, close to the MEN-1 gene. AIP mutations do not appear to play a prominent role in sporadic pituitary tumourigenesis.[4]
McCune-Albright syndrome
This syndrome is caused by activating G-protein mutations, frequently detected in the maternal allele, which is consistent with the mono-allelic imprinting of GNAS1 gene (the G protein Gs-alpha; termed gsp oncogene) in the pituitary. It is characterised by polyostotic fibrous dysplasia in the bones, precocious puberty, hyper-pigmented skin patches, and somatotroph hyperplasia, leading to acromegaly. GH excess is observed in up to 20% of patients.[6]
Carney complex
This autosomal-dominant disorder is due to inactivating germline mutations in protein kinase A regulatory sub-unit 1, which is important for intracellular protection against unrestrained catalytic sub-unit activity. This syndrome is characterised by spotty mucocutaneous pigmentation, cardiac myxomas, and primary pigmented nodular adrenocortical disease. Endocrine tumours, such as pituitary somatotroph adenomas, are relatively infrequent; however, GH and prolactin excess may be present in up to 79% of cases.[6]
Use of this content is subject to our disclaimer