Untitled Document

DOI: https://doi.org/10.15605/jafes.034.01.03


Malaysian Consensus Statement for the Diagnosis and Management of Acromegaly
Zanariah Hussein,* Mohamed Long Bidin,** Azmi Alias,** Muthukkumaran Thiagarajan,** Kartikasalwah Abdul Latif,** Jeyakantha Ratnasingam,*** Wan Juani Wan Seman,* Azraai Nasruddin*

*Hospital Putrajaya, Malaysia
**Hospital Kuala Lumpur, Malaysia
***University of Malaya, Kuala Lumpur, Malaysia

Corresponding Author

Zanariah Hussein, MRCP (UK)
Medical Department, Jalan P9, Presint 7,
62250 Putrajaya, Wilayah Persekutuan Putrajaya, Malaysia
Tel. No.: +603-8312 4200
Fax No.: +603-8888 0137
E-mail: zanariahh@hotmail.com
ORCiD: https://orcid.org/0000-0002-7367-2853


e-ISSN 2308-118x
Printed in the Philippines
Copyright © 2019 by the JAFES
Received March 27, 2019, 2018. Accepted May 14, 2019.
Published Online First: May 28, 2019.

ABSTRACT


In Malaysia, acromegaly is under-recognised with only 10-15% of the expected number of cases from prevalence estimates, having been diagnosed and managed in established endocrine centres with access to multidisciplinary care. This is mainly due to lack of awareness and standardised approach in diagnosing this disease resulting in delay in diagnosis and management with suboptimal treatment outcomes. This first Malaysian consensus statement on the diagnosis and management of acromegaly addresses these issues and is based on current best practices and latest available evidence so as to reduce the disease burden on acromegaly patients managed in the Malaysian healthcare system.

Keywords: acromegaly, consensus, Malaysia, growth hormone excess

INTRODUCTION

Acromegaly is an uncommon clinical syndrome resulting from excessive growth hormone (GH) production. In most cases, it arises from a GH secreting pituitary adenoma with resultant increased production of insulin-like growth factor-1 (IGF-1) from the liver. Both hormones exert characteristic changes and growth effects on major organ, skeletal and soft tissues. The resultant insulin resistant state, leads to predisposition of developing glucose intolerance, metabolic dysfunction and increased cardiovascular risk with associated co-morbidities such as hypertension, obstructive sleep apnoea (OSA) and arthritis. OSA in acromegaly is due to osseous and soft tissue changes which lead to narrowing and collapse of the upper airway during sleep. The pituitary tumour, typically a macroadenoma, can contribute to local mass effect with complications such as visual disturbance and hypopituitarism.

Main aims of treatment in acromegaly are to reduce and restore GH and IGF-1 levels to normal range, as this is associated with control of symptoms, prevention and control of complications, and reduction in morbidity and mortality. Treatment choices include surgical, medical and radiation therapy (RT) needing long-term multidisciplinary monitoring.

METHODOLOGY

This consensus statement is based on latest best practice recommendations of the Endocrine Society[1] and American Association of Clinical Endocrinologists (AACE)[2] guidelines, and a comprehensive review of current medical literature. The recommendations were then developed with consensus building through face-to-face meetings by a multidisciplinary group of Malaysian specialists involved in the care of acromegaly patients consisting of endocrinologists, neurosurgeons, radiologists, radiation oncologists and laboratory specialists. The local recommendations were then carefully formulated taking into consideration the Malaysian healthcare system and the local availability and accessibility of diagnostic procedures and management options for patients with this disease. This was then circulated to a group of external reviewers in the same specialities and practicing within Malaysia for further review and feedback, which were taken into consideration resulting in these final recommendations.

Epidemiology

Acromegaly is a rare disease with significant risk of mortality. Based on existing data from western countries, the prevalence of acromegaly is approximately 70-80 cases per million population (cpmp) and its incidence, 3-11 cpmp/year.[3],[4],[5],[6] However, data from some Asian countries have approximated the prevalence of acromegaly at 28 cpmp and its incidence at 4 cpmp/year.7 Males and females are equally affected by the disease.[3],[4],[7] The mean age of diagnosis is from mid-forties to early fifties[3],[7],[8],[9] however, there is an average of 4-7 years of delay in confirming diagnosis from the onset of GH hypersecretion.[3],[4],[10]

There are at present very limited Malaysian epidemiological data available for acromegaly. From unpublished observational data of the Malaysian Acromegaly Registry, acromegaly appears to be seriously under-recognised and under-diagnosed in the country, with fewer than 150 patients being managed at established endocrine centres. However, from the case series collected, the ratio of male to female is similar with other countries.

The most common cause of acromegaly, accounting for >95% of cases is GH-secreting pituitary tumours arising from somatotroph cells.[1] The majority of the pituitary tumours (70%) are macroadenomas (≥1 cm in diameter) whilst the rest are microadenomas (<1 cm in diameter).[3] In the hands of high-volume pituitary surgeons, patients with microadenomas are expected to have 80-90% chance of surgical cure.3 On the other hand, patients with macroadenoma are expected to have 40-50% chance of surgical cure. Achieving disease control in these patients with macroadenoma is challenging even with combination treatment of pituitary surgery, RT and medical therapy. These treatment options are notably costly, so a sensible and schematic selection of patients for specific modalities of treatment is paramount. It is important to note that individuals with uncontrolled disease have at least a 2-fold increase in mortality risk compared to the general population.[1],[11],[12],[13] The most common cause of mortality in acromegaly is from cardiorespiratory diseases.

Clinical features

The most common complaints bringing patients with acromegaly to consult their primary care doctors, that lead to further tests to confirm diagnosis are headache and acral enlargement.[14] The latter feature usually comprises of lower jaw enlargement and protrusion (prognathism) with dental malocclusion, overbite and interdental separation[15] and, increasing ring and shoe size.[10],[16]

Acromegaly is also associated with various co-morbidities. Data from the Malaysian Acromegaly Registry show that co-morbidities commonly encountered are diabetes mellitus, hypertension, cardiac diseases, OSA and multinodular goitre.

Other features that may be associated with acromegaly are visual field defects (typically bitemporal hemianopia), hyperprolactinemia, hypopituitarism (comprised of hypogonadism, hypothyroidism and hypocortisolism), colonic polyps, visceromegaly, carpal tunnel syndrome (CTS), large joint pains, oily perspiration (mainly noted by hand examination) and multiple skin tags.[16],[17]

Diagnosis

Clinical diagnosis

In the local context, if any clinician encounters a patient with acral enlargement of the face, hands or feet with two or more co-morbidities or features associated with acromegaly, biochemical screening is then indicated. The clinical features suggestive of Acromegaly include the presence or complaints of headache, diabetes mellitus, hypertension, heart disease of uncertain aetiology, OSA, colonic polyps, large joint pains, CTS, sweaty/oily hands or multiple skin tags.

In Malaysia, efforts have been carried out to educate primary care physicians regarding early recognition of clinical features of acromegaly. Regional level disease awareness talks by endocrinologists to primary care doctors have been carried out to highlight the disease and it’s comorbidities and complications and emphasising the need for earlier diagnosis at the primary care level. Promotional educational material have been developed in the form of posters and video clips and distributed to all government primary care clinics. A screening algorithm will also soon be introduced to ease and facilitate the referral pathway of suspected cases of Acromegaly to receive prompt review by an endocrinologist at the nearest hospital.

Biochemical diagnosis

Biochemical screening should be performed promptly where clinically indicated and serum IGF-1 assessed if the test is available and accessible. In Malaysia, serum IGF-1 testing is limited and only available at endocrine laboratories at a single central government hospital, few university hospitals and private hospitals. Where the test is not accessible, referral should be made to an endocrinologist for biochemical screening and confirmation of acromegaly. Serum IGF-1 is measured as an initial screening test as it is the most sensitive and specific test for diagnosis. The levels should be interpreted using assay-specific age and gender matched reference ranges developed by the assay manufacturer. In Malaysia, different laboratories are using different assays which result in differences in the reference ranges. There are also various conditions that may elevate (e.g., puberty, pregnancy and hyperthyroidism) or lower (e.g., malnutrition, liver failure, renal failure, oral oestrogen use, untreated hypothyroidism and uncontrolled diabetes) serum IGF-1 levels. Interpretation of results will need careful consideration of the clinical context of the patient.[18],[19]

An oral glucose tolerance test (OGTT) in patients with elevated IGF-1 that fails to suppress GH confirms diagnosis of acromegaly. At times it is justified to proceed simultaneously with an OGTT without waiting for IGF-1 levels in patients with a very high index of clinical suspicion to minimise diagnostic delay. The nadir GH level is seen between 60-120 minutes following an oral glucose load thus, GH measurements are recommended to be taken at 0, 60 and 120 minutes during the OGTT2,[20] and failure to supress GH levels to <1 mcg/L during OGTT (at 120 minutes) is considered diagnostic of acromegaly.[1]

There are instances however, where there may be discordance in IGF-1 and GH levels, i.e., elevated IGF-1 with nadir GH <1mcg/L during OGTT. With improvement in the sensitivity of modern GH assays, it has been established that in normal individuals, the nadir GH is <0.3 mcg/L.[21] Depending on the sensitivity and accuracy of the GH assay used, some authorities advocate using a cut-off of 0.4 mcg/L during an OGTT to diagnose acromegaly.[2] Therefore, when a highly sensitive GH assay is used in the context of an elevated serum IGF-1, a nadir GH above 0.4 mcg/L is consistent with a diagnosis of acromegaly. Discussion with a laboratory biochemist is required to establish sensitivity of GH assay in use.

Random GH or mean GH levels are not suitable or recommended to be used for making the initial diagnosis of acromegaly due to poor specificity.[1]

Imaging

Magnetic resonance imaging (MRI) of the pituitary (MR pituitary) with and without contrast is the neuroimaging investigation of choice in patients with acromegaly confirmed by biochemical diagnosis. All patients with likely exposure to contrast agents should have their serum creatinine and estimated glomerular filtration rate (eGFR) tested to identify individuals that are at potential risk of developing contrast induced nephrogenic systemic fibrosis. Patients with eGFR <30 ml/min/1.73m2 should not have contrast administered.

MR pituitary is the preferred diagnostic imaging modality to evaluate sellar and parasellar tumours, offering high contrast and multiplanar thin cuts[22] which enable the evaluation of small soft tissue changes.

MR pituitary protocols should include pituitary sequences, 3 mm thick slices with Coronal T1WI /T2WI /T1 post-gadolinium and Sagittal T1WI /T1 post-gadolinium with or without a dynamic study. Optional added brain sequences include, T2WI axial and T1 axial post-contrast sequences. A dynamic MR pituitary may be useful particularly when functioning microadenomas are suspected as, it obtains images within seconds after administration of gadolinium.[23]

Computed tomography (CT) scan of the pituitary is only suggested in patients where MRI is contraindicated, as anatomical details are less defined.[2] Locally, this is already less commonly done. However, if necessary, CT should be done with use of contrast and must include multiplanar reformats.

Management

The management of acromegaly involves multimodal therapy.[1],[2],[24],[25] Individualised treatment decisions should ideally be made following multidisciplinary team (MDT) discussions involving endocrinology, neurosurgery, neuroradiology, oncology, ophthalmology and pathology specialities. Hence, the management of acromegaly patients in Malaysia should be centred in major public, university and private hospitals with availability of specialists in these disciplines.

The main goals in acromegaly treatment[1],[2] are tumour shrinkage, reduction of GH (<1 mcg/L) and normalisation of IGF-1,[26] resolution of clinical symptoms, improvement in co-morbidities and reduction in long-term mortality.

Surgery, is the recommended first line treatment1,2 of acromegaly. Medical therapy with somatostatin receptor ligands (SRL) and dopamine agonists (DA) such as cabergoline are also available.

Locally, despite advancements in surgical techniques and medical therapy, RT[27] still has an important role as salvage therapy. Indications for RT include patients unfit for or who refuse surgery, residual or recurrent tumours not amenable to repeat surgery or failed medical therapy.[27],[28]

Surgery

In Malaysia currently, most patients diagnosed with acromegaly, are recommended trans-sphenoidal surgery as the first line of treatment followed by medical therapy and RT, should surgery not be curative.[1],[2],[29] A well-coordinated multidisciplinary team approach in the surgical management of acromegaly can offer optimal treatment with better outcomes and lower morbidity.[1]

The goal of surgery is to achieve cure and to avoid life-long post-operative hormonal replacement therapy. Aggressive and complete removal of GH secreting tissue is therefore advocated whenever possible, whilst attempting to identify and preserve the remaining normal pituitary tissue.[2]

The ability to rapidly normalise GH and IGF-1 levels, compared to medical and RT, makes trans-sphenoidal surgery (TSS) the treatment of choice.[29] For large and invasive tumours, debulking surgery is suggested to relieve compressive symptoms and to enhance response to medical therapy.[1],[2] Therefore, it is also advocated in patients where surgical cure is not feasible due to tumour location or invasiveness.[29] Repeat surgery is recommended when there is elevated IGF-1 in the presence of an accessible residual or recurrent tumour.

Pre-operative evaluation should consist of imaging and management of co-morbidities. MRI is the recommended imaging modality of choice for pre-operative evaluation and surgical planning followed by dynamic contrast-enhanced multisection CT scan when MRI is contraindicated or not available. High resolution MRI with pituitary protocol helps in localising the tumour and visualising fine anatomic details surrounding the tumour and its neighbouring structures as well as presence of haemorrhage or tumour necrosis. MRI for Image Guided Surgery protocol is recommended for removal of macroadenoma with cavernous sinus invasion, destruction of sellar floor, poor pneumotisation of sphenoid sinus, repeated surgery and microadenoma with normal size sellar turcica.

On the other hand, computer assisted imaging navigation provides a pre-operative and intraoperative 3-dimensional (3-D) mapping of tumour margins in relation to surrounding tissues which, can be useful during the pre-operative planning. It serves as a guide to safe resection whilst preserving critical functions, ensuring patient safety and improving outcomes. Additionally, high resolution CT scan may be required in the presence of significant bony enlargements within the nasal cavity and skull base to determine the necessity of an adjunct endonasal surgical procedure.

Selective adenomectomy via trans-sphenoidal-trans-nasal route should be the preferred surgical technique as it emphasises targeted and minimally invasive approaches. This is done by using either an operating endoscope or microscope for visualisation and microsurgical techniques.[1],[2]

For tumours that are not visualised well on MRI, the possibility of an ectopic neuroendocrine tumour producing GHRH should be considered, even though very rare. For those undergoing transphenoidal surgery with unidentifiable tumour intraoperatively despite confirmative biochemical analysis, partial hypophysectomy may be considered. In failed remission, a more aggressive approach during repeat surgery may be required. Other alternative approaches can include conventional microscopic sublabial trans-septal approach and endoscopic assisted trans-nasal microsurgery.

For large tumours with significant extension to suprasellar, intraventricular, lateral, parasellar or fronto-temporal regions, cavernous sinus invasion or involvement of critical neurovascular structures, transcranial surgery is recommended. In large and invasive tumours, multiple approaches may be required.

Reconstruction of the sellar defect after tumour removal with vascularised mucoperiosteum-mucoperichondrium nasoseptal flap is recommended for large defects or in the presence of an intraoperative cerebrospinal fluid (CSF).

Additionally, Image Guided Surgery protocol is strongly recommended when normal anatomical landmarks of the nasal cavity and endonasal skull base are altered or destroyed by a large tumour or previous surgery.

Medical therapy

SRL is offered as secondary treatment in the presence of residual disease without mass effects after primary surgery.[1],[2],[25] As long-term indefinite use of SRL is heavily limited by its cost in the Malaysian setting, most patients are offered other definitive treatment options such as repeat surgery and/or RT. As such, the most common indication of SRL would be as bridging therapy while awaiting the effects of RT or to control co-morbidities while awaiting the second surgery.

SRL is also an option as primary medical therapy in macroadenomas with extrasellar extension particularly into the cavernous sinus, without mass effect or chiasmal compression where surgical cure is unlikely.[1],[2] Other indications of SRL as primary therapy should be in patients who are poor surgical candidates (e.g., age and co-morbidity restrictions)[1],[2] and those who refuse surgery. As a pre-operative treatment, SRL has limited use to those with severe pharyngeal thickness, sleep apnoea or heart failure to improve surgical outcomes.[1],[30]

The two commonly used SRL in Malaysia are the intramuscular (IM) octreotide long-acting release (LAR) and subcutaneous (SC) lanreotide depot formulations that are administered four weekly. IM octreotide LAR is available in 20 mg and 30 mg doses and SC lanreotide is only available in 120 mg dose formulation. Most physicians in Malaysia do not use a test dose of short acting (SA) octreotide prior to commencing the long-acting formulation. In terms of efficacy, both octreotide LAR and lanreotide are similar[1],[2],[31] with an expected GH control to safe levels (<2.5 mcg/L) and/or IGF-1 normalisation in 34-55% of patients.[32],[33],[34],[35],[36] With SRL, a clinically relevant reduction in tumour volume (>20%) is seen in 53-63%[37],[38] of patients.

SC lanreotide has an added benefit of convenience in a pre-filled ready to use pen that allows partner or self-injection39 compared to IM octreotide LAR which requires reconstitution and administration by a healthcare professional. With improvement in clinical, biochemical parameters and reduction in tumour size, physicians may extend the dosing intervals up to 8-12 weekly for octreotide LAR and 6-8 weekly for SC lanreotide in order to improve cost effectiveness.[40],[41] However, if SRL standard dosing does not achieve control, the frequency may be increased to every 3-weekly (for lanreotide 120 mg and octreotide 30 mg) for better disease control.[42],[43] The main adverse events are abdominal cramps and diarrhoea that are usually temporary. However, more severe side effects such as formation of gall bladder sludge and stones require an abdominal ultrasound only if patients present with symptoms of gall bladder disease.[1]

Pasireotide LAR, a second generation SRL can be used in selected cases when octreotide LAR or lanreotide fail to control IGF-1, as data show better efficacy with this agent.[35],[44],[45] However, its use is limited by very high cost and to patients without poorly controlled glucose, as there is a high rate of worsening hyperglycaemia seen in up to 70% of treated patients.[35] Though pegvisomant, the GH receptor antagonist is the most effective medical therapy for acromegaly[46] it is currently unavailable in Malaysia.

DA is another option in medical therapy for acromegaly. It is mainly used for mild residual disease (IGF-1 <2 times upper limit of normal; ULN)47 or when cost limits the use of SRL, and has the added benefit of being orally administered. DA is used regardless of prolactin co-secretion. Though accepted as a less effective form of treatment, these drugs may be used in Malaysia as bridging therapy as it is less costly in comparison to SRL. Cabergoline is the only DA that has been widely studied and recommended for use in acromegaly[47],[48] with 30% of patients reaching normalised IGF-1 when used as a single agent. The dose of cabergoline is between 1.5-3.5 mg/week and patients should be warned of its side effects such as nausea, hypotension and headaches prior to initiating treatment. All patients on cabergoline should have an annual clinical cardiovascular examination to detect valvulopathy.[49] Echocardiogram (ECHO) should be reserved for patients with audible murmur, on cabergoline ≥3 mg/week for more than five years or equivalent cumulative dose, and those who maintain treatment after the age of 50 years.[49]

Combination treatment with SRL and DA is recommended in patients who have only partial control with SRL monotherapy[50],[51] with 42-44% of patients uncontrolled on single therapy reaching normal IGF-1 levels with combination therapy.[2],[50] Generally considered a weak agent, selective oestrogen receptor modulators (SERMs) or oral oestrogen[2],[52] may be used in combination with SRL and DA. This may be an option in patients with mild disease who cannot afford the use of SRL. However, this combination is not commonly practiced in Malaysia and experience is therefore limited.

Radiotherapy

Indications for intensity modulated radiotherapy (IMRT), fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS) are normally reserved for residual or recurrent tumour cases where risk of surgery is high or when patients refuse surgery. RT services including FRST are available in four out of five Ministry of Health, Malaysia centres. IMRT is available in all centres whilst SRS is offered in Kuala Lumpur General Hospital and the National Cancer Institute. Therefore, fractionated RT with 1.8-2 Gray (Gy) per day (up to a total dose of 50.4-54 Gy) is the recommended standard approach toward irradiating secreting pituitary adenomas. This results in tumour growth control in 80-90% and normalisation of GH/IGF-1 in 50-60% of patients at 10 years.[53] Rapid decrease in GH occurs in the first two years followed by progressive, slow decrease over 10-20 years.[54] Median onset of biochemical remission is between 7-10 years.[55] Hypopituitarism occurs in up to 60% of treated patients and its onset follows a similar time course as the development of remission. Optic neuropathy (1-5%), brain necrosis (<1%), cerebrovascular accident and second intracranial neoplasms (1-2%) are long-term side effects that should be followed up.[55] Fractionated RT should be delivered using 3-D conformal radiation technique with CT image acquisition53 and is consistent with local practice. IMRT and FRST are preferred, as it significantly reduces dose of radiation to normal tissues and incidence of long-term toxicities.[55]

SRS is preferred56 if appropriate equipment such as linear accelerator, gamma knife or Cyberknife, and trained personnel are available. Minimum distance of tumour to optic chiasm of 3 mm needs to be fulfilled for this approach to be possible.[53] A margin dose of 18-25 Gy is recommended. Though long-term tumour control rate of 80-90%, similar to fractionated RT, is achievable, its strength lies in earlier normalisation of GH/IGF-1 as early as 1.4 years (median 4.5 years).[55] Risk of long-term side effects are further reduced, even though hypopituitarism still remains common reaching up to 50% in some case series.[28],[53]

As data is conflicting in different case series,[54],[55] interruption of somatostatin analogue during RT should not be routinely adopted in our setting. Patients who have received RT should be monitored with GH/IGF-1 and hormonal profiles annually.[1]

Monitoring

GH and IGF-1 levels should be monitored to assess treatment efficacy and to detect persistent or recurrent disease. Regular assessment of possible development of hypopituitarism, co-morbidities and complications should be carried out.

Post-surgical monitoring

Monitoring patients post-surgery should include both biochemical and imaging studies. The recommendation for IGF-1 level and random GH measurements is at 12 weeks post-surgery.[1] Immediate post-operative measurement of GH is not recommended in the local context. GH value of <1 mcg/L at 12 weeks and a normal IGF-1 value (after age-dependent normalisation) by 3-6 months are consistent with surgical remission.[2] GH level <1 mcg/L indicates “control” and normalisation of mortality risk.[1],[57] If the GH is >1 mcg/L, we suggest to measure nadir GH levels after an OGTT.[1]

Following a surgical cure, all patients should have at least an annual IGF-1 level with the addition of OGTT if there is any suspicion of recurrence clinically or based on IGF-1 levels.[2],[57] Although most cases have concordant GH and IGF-1 levels, discordant levels can be seen in about 35% of patients with active acromegaly.[58] A repeat testing of GH and IGF-1 levels is suggested 3-4 months after a discrepant result.[59] However, there is no specific guideline on the management of patients with discordant GH and IGF-1 levels.

The first post-surgical MR pituitary should be done at least 3-4 months after the surgery[2],[60],[61],[62] and subsequently based on disease activity.[2] In patients with pre-operative visual field defects, visual field testing should be done regularly post-surgery.[1]

As there is no available consensus on frequency of post-operative pituitary hormone assessment, based on current local practice, we recommend that it be performed at 3- and 6-months post-surgery and annually thereafter. Hypopituitarism is a significant complication of either continued tumour growth compromising normal pituitary function, or consequences of loss of pituitary function post-surgery or post-radiotherapy.

Monitoring patients receiving medical therapy

For patients who are on medical treatment with SRL or DA, it is recommended to monitor both GH and IGF-1 levels to assess response to treatment. GH and IGF-1 levels should ideally be monitored 4-6 weeks after any dose change.[2] It is also recommended to monitor adverse events associated with SRL such as gastrointestinal and metabolic disorders.

OGTT should not be used to monitor treatment response to SRL, as it is unreliable. Disease monitoring should be done using IGF-1 and random GH levels.[63]

Monitoring patients receiving radiotherapy

Patients receiving RT are at risk of developing hypopituitarism, radiation-induced secondary tumours and radionecrosis. The recommendation is for annual assessments to evaluate pituitary function for hypopituitarism and monitoring of GH and IGF-1 levels.[2],[57] Visual acuity and visual field should be closely monitored by regular formal testing to assess any damage to the optic chiasm or optic nerves following RT.

Monitoring of co-morbidities

Cardiovascular and cerebrovascular events are the main causes of death in patients with acromegaly. Cardiovascular risk factors should be appropriately treated and monitored.

Patients with symptoms of OSA should have an overnight polysomnography done. ECHO and electrocardiography (ECG) should be performed in patients with suspected cardiac disease. Screening for hypertension and diabetes should be regularly performed.

Patients should also be monitored for signs and symptoms of CTS and arthropathy whilst bone densitometry should be performed in patients with history of hypogonadism or fractures.[2] All patients should undergo colonoscopy once diagnosed with acromegaly[1],[2] and repeated either every five years in patients with a colonic polyp at screening or with persistently elevated IGF-levels, or 10 years in those without any polyps at screening and controlled disease.[1] Ultrasound of the thyroid should be performed if there is palpable thyroid nodularity1 in view of increased risk of thyroid cancer in acromegaly.[64]

CONCLUSIONS

There are significant challenges in the management of patients with acromegaly in Malaysia. There need to be better awareness of the condition among primary care doctors and other specialities due to the heterogeneity of GH-related morbidity presentation. There is a need for improved screening to identify patients and earlier referral to endocrinologists for confirmation of diagnosis and treatment initiation.

A multidisciplinary team should assess each newly diagnosed acromegaly patient to ensure individualised plan of treatment. Comprehensive care and follow-up should be accessible via a dedicated pituitary clinic led by an experienced endocrinologist, with access to neuroimaging and endocrine laboratory facilities that provide appropriate assays for prompt measurements of GH and IGF-1.

This consensus has been developed to standardise the management of this uncommon disease in Malaysia. A prompt and optimal resource allocation and utilisation for the management of acromegaly will enable patients to achieve a good quality of life with reduction of chronic complications and co-morbidities. Ultimately, this strategy will contribute to true cost savings and reduce this disease burden on the Malaysian healthcare system in the long-term.

Statement of Authorship

All authors certified fulfillment of ICMJE authorship criteria.

Author Disclosure

The authors declared no conflict of interest.

Funding Source

None.

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