Lavrentaki A, Paluzzi A, Wass JA, Karavitaki N. Epidemiology of acromegaly: review of population studies. Pituitary. 2017; 20:4-9 https://doi.org/10.1007/s11102-016-0754-x
Gosau M, Vogel C, Moralis A, Proff P Mandibular prognathism caused by acromegaly – a surgical orthodontic case. Head Face Med. 2009; 5 https://doi.org/10.1186/1746-160X-5-16
Melmed S, Bronstein MD, Chanson P A consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018; 14:552-561 https://doi.org/10.1038/s41574-018-0058-5
McKenna G, Hayes M, Burke FM. Prosthodontic rehabilitation for a patient with acromegaly. Eur J Prosthodont Restor Dent. 2014; 22:98-100
Sugata T, Myoken Y, Tanaka S. Acromegaly identified in a patient with a complaint of malocclusion. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998; 85:44-46 https://doi.org/10.1016/s1079-2104(98)90396-1
Bekri S, Trifi W, Labidi A, Bizani C, Mansour L. Full-mouth rehabilitation of an acromegaly disease patient with removable prostheses: a clinical case report. Pan Afr Med J. 2019; 33 https://doi.org/10.11604/pamj.2019.33.5.18194
Atreja G, Atreja SH, Jain N, Sukhija U. Oral manifestations in growth hormone disorders. Indian J Endocrinol Metab. 2012; 16:381-383 https://doi.org/10.4103/2230-8210.95678
Kernen FR, Bidra AS. Dental implant therapy in a patient with acromegaly: a clinical report. J Prosthodont. 2019; 28:355-360 https://doi.org/10.1111/jopr.13043
Sharma G, Amin D, Shorafa M. Challenges in the management of late developing malocclusions in adulthood: a case report of acromegaly. J Orthod. 2019; 46:349-357 https://doi.org/10.1177/1465312519869943
Siegel S, Streetz-van der Werf C, Schott JS Diagnostic delay is associated with psychosocial impairment in acromegaly. Pituitary. 2013; 16:507-514 https://doi.org/10.1007/s11102-012-0447-z
Agrawal M, Maitin N, Rastogi K, Bhushan R. Seeing the unseen: diagnosing acromegaly in a dental setup. BMJ Case Rep. 2013; 2013 https://doi.org/10.1136/bcr-2013-200266
Humerfelt A, Reitan K. Effects of hypercementosis on the movability of teeth during orthodontic treatment. Angle Orthod. 1966; 36:179-189
Ozdemir Y, Keceli HG, Helvaci N The tendency of reduced periodontal destruction in acromegalic patients showing similar inflammatory status with periodontitis patients. Endocrine. 2019; 66:622-633 https://doi.org/10.1007/s12020-019-02060-2
Acromegaly is a progressive, multi-system disease caused by excessive growth hormone production that, if untreated, may lead to significant morbidity, mortality and impact on a sufferer's quality of life. Changes to the orofacial complex are a prominent feature of the disease, meaning the dental profession is in a unique position to be able to recognize the condition early. This article discusses its presentation, diagnosis and management with a particular focus on the potential effects on the orofacial complex, leading to an exploration of the difficulties that may be encountered when dental rehabilitation is required.
CPD/Clinical Relevance: Dental professionals may be the first to recognize the orofacial changes associated with acromegaly.
Article
Acromegaly is an endocrine disease caused by excessive production of growth hormone (GH) inducing increased production of insulin-like growth factor-I (IGF-1), which, in more than 95% of cases, is due to a benign adenoma of the pituitary gland.1,2 It is differentiated from gigantism by the condition developing in adulthood, defined as subsequent to the closure of the epiphyseal plates which occurs typically between the ages of 12 and 16 years or girls and 14 and 19 years for boys.1
While rare, there is significant population variability of the disease. A review of the epidemiological data demonstrated an incidence of 0.2–1.1 cases per 100,000 of the population and a prevalence of 2.8–13.7 cases per 100,000.3 There appears to be no difference in prevalence between males and females, with the average age at diagnosis between 40 and 50 years old.1 This late apparent onset may be, at least in part, due to the effects typically being insidious, leading to an average delay in diagnosis after condition development of between 4 and 10 years.1,2,4 Despite the chronic nature of the disease, there is significant associated morbidity and mortality, with an estimated reduction in life expectancy of 10 years if left untreated.2,5
The wide range of effects of the disease are a result of both local tumour expansion and prolonged exposure of various organ systems to persistently high levels of GH and IGF-1. These effects are discussed in more detail below and summarized in Table 1.
Local effects
Headaches, visual disturbance
Systemic effects
Extremities
Hand enlargement, foot enlargement
Skin
Thickening, hyperhidrosis, seborrhoea
Cardiovascular system
Left ventricular hypertrophy, atrial hypertension, cardiomyopathy, arrhythmia, congestive heart failure
Respiratory system
Snoring, obstructive sleep apnoea
Musculoskeletal system
Arthralgia, myalgia
Metabolic
Diabetes mellitus
Neoplasia
Bowel cancer, thyroid cancer
Other
Deepening voice, slowing of speech
Orofacial effects
Thickening of lips/nose/ears, forehead bossing, prognathism, development or exaggeration of Class 3 skeletal or incisor pattern, increased occlusal vertical dimension, anterior open bite, drifting of dentition, interdental spacing, tooth mobility, hypercementosis, macroglossia
Local effects of tumour
Headaches: these may be severe and disproportionate to the size of the tumour, affecting around 60% of patients.1
Visual disturbances: expansion of the tumour superiorly will lead to pressure on the optic chiasm, leading to visual disturbances and eventually blindness if the compression persists.1
Systemic effects of tumour
Cardiovascular system: left ventricular hypertrophy and atrial hypertension are most commonly seen; however, cardiomyopathy, arrhythmia and congestive heart failure are also associated with the condition.1,2 The effects on the cardiovascular system have historically accounted for the majority (60%) of mortality.2
Respiratory system: macroglossia and hypertrophy of the palatal tissues result in a predisposition to snoring and obstructive sleep apnoea,6 with the latter also linked to morning fatigue and lethargy.2 Hypertrophy of the laryngeal tissues and frontal sinuses may lead to a deepening of the voice,1,2 and a slowing of the speech may occur.7
Metabolic complications: excess GH is linked to glucose intolerance and the development of diabetes mellitus in 20–56% of patients.2
Neoplastic complications: acromegaly patients have a notably higher incidence of bowel and thyroid neoplasia,6 with the former even replacing cardiovascular complications in some recent studies as the main cause of mortality.1
Skin and periphery: soft tissue overgrowth is present in the overwhelming majority of patients, leading to the characteristic ‘spade-like’ appearance of the hands and feet. A history of size change affecting the wedding ring, gloves and shoes is a common complaint (Figure 1).1,2,8 Patients may also develop oily skin (seborrhoea) and increased sweating (hyperhidrosis).1,2
Figure 1.
(a, b) Both parts demonstrate examples of thickening of the soft tissues of the hands of two different acromegaly patients leading to the classic ‘spade-like’ appearance. Note in (b) the patient unable to fully seat their wedding ring due to the significant enlargement that has occurred.
Musculoskeletal system: arthralgia and myalgia have been noted to affect a significant proportion of patients and may affect any joint.1,2
Orofacial changes
Orofacial changes can range from the subtle to the obviously disfiguring,9 and while they do not affect life expectancy, they have been found to have the biggest impact on the reported reduction in quality of life of patients.10
Increased collagen synthesis causes thickening of the tissues, especially noticeable in the nose, lips and ears. Thickening of the skin overlying the forehead in combination with proliferation of the bone of the supra-orbital region leads to the appearance of frontal bossing (Figures 2 and 3).2
Figure 2. Front view of patient displaying characteristic facial changes associated with acromegaly. Note the thickening of the soft tissues of the nose, lips and forehead, the latter leading to significant creasing of the forehead.Figure 3. Profile view of acromegaly patient displaying characteristic thickening of the tissues of the supra-orbital region leading to frontal bossing.
However, bone growth is usually most profound in the condyle and ramus, causing thickening and widening of the mandible leading to mandibular prognathism, tooth drifting, interdental spacing and malocclusion (Figure 4).9 It has been reported that 16–57% patients exhibit mandibular prognathism, with an average increase in protrusion of 9.3 ± 3.4 mm,11 and a Class 3 occlusion being recorded for up to 77% of patients in another study.12
Figure 4.
(a–c) Intra-oral views of acromegaly patient showing classic Class 3 occlusion with bilateral buccal cross bite present. Notice the significant drifting of the LL7 out of the arch.
Macroglossia is very common and constitutes another contributory factor to drifting of teeth, their proclination labially or buccally, and also to interdental spacing.10 This most commonly affects the mandibular teeth, especially the anterior teeth, which have also been noted to be predisposed to developing mobility.13 If the macroglossia is significant, it may also result in the patient reporting difficulties when eating and speaking.8
Hypercementosis may be seen radiographically and if present, usually affects the posterior molar teeth (Figure 5).14 It has been proposed this is because of increased functional loading due to malocclusion and muscular hypertrophy,9,13 but it should be noted that this has been disputed as the pathological cause.15
Figure 5. Intra-oral radiograph displaying classic bulbous appearance of radicular hypercementosis affecting the LR3.
Diagnosis
Diagnosis is via biochemical testing demonstrating elevated levels of GH and IGF-1. However, as even healthy patients can sporadically produce excessive amounts of GH, the blood sample is taken only after an oral glucose tolerance test is performed.2 CT or MRI scanning is used to assess for the presence and extent of a pituitary tumour. An incidental lateral cephalometric radiograph would classically show an enlarged sella turcica as a result of tumour growth.4,16
Treatment
The first line of treatment is usually surgical.2,6 A trans-sphenoidal approach is normally used via an incision under the upper lip or inside the nose and the tumour resected endoscopically. This should result in an immediate drop in unwanted hormone production and is successful in 50–67% of cases.4 If surgery is not successful in reducing hormone levels, or if complete resection was not attempted because of the risk to adjacent anatomical structures, then the next line of treatment is usually a somatostatin analogue, GH-receptor antagonist or dopamine agonist.2 Radiotherapy is usually reserved as a last resort because of its delayed effect and the risk of collateral damage to the pituitary gland and adjacent structures.
If the circulating GH and IGF-1 levels are successfully controlled, then the soft tissue changes may recede and normalize gradually. Bony or dental changes will not spontaneously correct and are the main cause of only mildly improved quality of life scores regarding appearance reported after treatment.10
A self-assessment questionnaire completed by 145 acromegaly patients saw 81% of responders reporting some form of orodental abnormality with just over half of these patients actively seeking dental treatment.10 This outcome figure is similar to another study that found that more than one-third of acromegaly patients developed signs or symptoms that prompted a dental appointment prior to their diagnosis.17 Indeed, Agrawal et al state that of healthcare professionals, dentists may account for approximately 40% of initial acromegaly diagnoses,18 a finding echoed elsewhere.14 The most common reasons for acromegaly patients to seek a dental opinion were macroglossia, interdental spacing, malocclusion, ill-fitting dentures and mandibular prognathism.10,14
This all serves to highlight the opportunity dentists and dental care professionals may have in ensuring as early a diagnosis as possible. It has been suggested that a formal diagnosis be completed within 2 years of onset to ensure minimal orofacial alteration and so guarantee as little disruption as possible to the individual's quality of life.10
Impact of orofacial changes on dental management
Depending on the severity of the orofacial changes and the patient's aesthetic concerns, dental treatment may range from simple maintenance to complex, multidisciplinary rehabilitations that present some specific challenges to achieving a successful outcome.
Mandibular changes
Depending on its severity, mandibular growth may result in a Class 3 incisor pattern, a Class 3 skeletal pattern, an increase in occlusal vertical dimension or teeth drifting and splaying, leading to potentially significant interproximal spacing and malocclusion.14,15,18 A decision needs to be made in concert with the patient, and where appropriate, an orthodontist and oral and maxillofacial surgeon as to which of the following is the most suitable course of action: simple maintenance; restoration within the limitations of the current skeletal pattern (likely to result in a compromised aesthetic result); a combination of treatment culminating in an osteotomy (if this is required or even desired).
On a more basic level, increases in the size of the mandible may present obstacles to achieving even basic tasks. Bekhri et al describe being unable to record primary impressions for a removable prothesis due to insufficient stock tray size.12 The issue was overcome by using hand-moulded silicone as a primary impression to allow later special tray construction.
Maxillary changes
There seems to be consensus in the literature that the maxilla exhibits little to no bony change,4,12 but significant thickening of the palatal soft tissues extending back to the uvula can occur.2 This may have an impact on the fit of removable maxillary prostheses and affect them again if successful control of GH levels results in a reduction in soft tissue bulk, necessitating relines or new prosthesis construction.7
Where the intra-oral soft tissue changes cause significant snoring or obstructive sleep apnoea, then referral to an ear nose and throat surgeon may be appropriate.
Bone quality
While increased IGF-1 and GH levels are associated with increased bone turnover due to increased osteoblast and osteoclast activity, there are conflicting reports in the literature regarding the possible negative impact on overall bone quality.15
Consequently, where implants are to be used, it must be appreciated that, although cortical bone is likely to be thicker, the quality of the underlying trabecular bone may be variable, and therefore will have an impact on the ease of placement and whether primary stability would permit immediate loading, if desired.
Hypercementosis
The usual difficulties associated with hypercementosed teeth may be encountered where extractions or orthodontic tooth movements of affected teeth are proposed.19 It should also be noted that any orthodontic tooth movement may be slowed down in general in the presence of a possible vitamin D deficiency leading to slower bone turnover.16
Periodontium
As discussed previously, acromegaly patients are at increased risk of developing diabetes, itself a well-accepted predisposing factor to the development of periodontal disease. However, there is a body of evidence that suggests GH and IGF-1 may actually have a protective effect on the destruction of the periodontal apparatus,13 although there is still some debate in the literature.20
Macroglossia
An enlarged tongue may have a significant impact on the provision of any mandibular removable prosthesis. It may be advantageous to consider having the prosthetic teeth set up in buccal cross-bite to allow more space for the tongue and so increase the stability and retention of the denture provided.12 Where orthodontics has been undertaken, the potential forces exerted by an enlarged tongue must be taken into account when considering post-treatment retention.16
Systemic disease
As with any patient, general health and any known comorbidities need to be taken into account, especially when any surgical intervention is being considered, such as implant placement or orthognathic surgery. It should therefore be highlighted that bisphosphonate therapy may be used as part of the medical treatment of acromegaly, meaning that relevant patients need to be appropriately counselled regarding the risk of medication related osteonecrosis of the jaw (MRONJ).15
Timing of treatment
The rare nature of the disease means there is minimal guidance in the literature concerning the appropriate timing of surgical interventions once hormone levels are stabilized. Sugata et al and Gosau et al recommend waiting 1 year and 2 years, respectively, before mandibular osteotomy surgery is undertaken.4,8 Only one paper could be found discussing dental implant use in an acromegaly patient,15 but the time period between hormone stabilization and fixture placement was not discussed. In any case, it is vital to have input from the patient's endocrinologist before any surgical intervention is performed.1
Recurrence
With pituitary adenoma recurrence reported to be 10–35%, any patient undergoing active treatment, be it prosthetic, surgical or orthodontic, must be fully aware of the risk of future relapse if long-term hormonal control is not achieved.7 However, it would be hoped that the effect of any recurrences are minimized by early detection and treatment because these patients will usually have life-long endocrinology monitoring.
Conclusion
Acromegaly is a rare condition, but its effects on the dentofacial complex may be profound and negatively impact a patient's quality of life. The dental profession should be aware of the clinical features of this disease, both to aid early diagnosis and to appreciate the possible challenges encountered if any surgical, orthodontic or prosthetic treatment is undertaken.
