Acromegaly-A case report

Acromegaly is a disorder characterized by Growth Hor­mone (GH) hypersecretion, multisystem-associated mor­ bidities, and increased mortality. Growth hormone is secreted by anterior part of the pituitary gland and it influences the growth of bone and soft tissue. Hypersecretion or hyposecretion of this hormone has a marked influence on the normal development of an individual. It also has marked influence on the development of oro-facial features, including the align­ ment of teeth, and mandibular prognathism, which compromises the aesthetics of an individual. Hence dental professionals have a role in diagnosing this disorder. We present here, a case report of Acromegaly.


Introduction
The word acromegaly comes from the Greek words acro for "extremities" and megaly for "enlargement".Acromegaly is a hormonal disorder that results from excessive secretion of growth hor mone (GH) in the body (1) .Growth hormone is secreted by anterior part of the pituitary gland (2) .The preva lence is about 7 cases per 100,000, with an annual in cidence of 0.3 cases per 100,000 (3) .
In acromegaly, the pituitary gland produces exces sive amounts of GH.In more than 95 percent of peo ple with acromegaly, a benign tumour of the pituitary gland, called an adenoma, produces excess GH.These adenomas are diagnosed in middle age and show an equal predilection for both the genders.The most se rious health consequences of acromegaly are type 2 diabetes, high blood pressure, increased risk of cardio vascular disease, and arthritis.Gradually, bone chang es alter the patient's orofacial features which are man ifested as thickening of the eye brow, elongation of lower jaw, enlargement of nasal bone, and spacing between teeth (3) .

Case History
A 54 yrs.male patient visited the outpatient department with the complaint of difficulty in chew ing, and protruding lower jaw, since 1 year.The changes were insidious in onset, progressed slowly and were associated with gradual change in voice, growth of extremities, general tiredness and exces sive sweating.These were associated with coarsen ing of facial features which compromised his aesthet ics.There was no associated pain in the jaw or joints.Medical/surgical history revealed that he had undergone transnasal transphenoidal surgery for pituitary tumour 1 ½ years back which was then diagnosed as macroadenoma.He had been under medication following surgery for five to ten days.( Tab..Eltroxin-0.1mg(Levothyroxine sodium) once daily, Tab.Wysolone -5mg (Prednisolone) once daily, Tab oflox-200mg once daily( Ofloxacin), Inj.Hu malong R 20units(Insulin), Inj.Lantus 8 units (Insulin).Tab.Piozone -15mg (Pioglitazone), Cap.Becosules (B-complex) once daily.)He was also diag nosed with hypertension, hyperglycemia, and hyper thyroidism.Extra oral clinical examination revealed facial asymmetry, lip incompetence, mandibular Quick access Code prognathism, and retrusion of maxilla, proptosis, prominent nose and supraorbital ridges.Skin over the forehead appeared thickened.Fingers and toes appeared large and broad.Intraoral examination revealed, macroglossia, Angle's class-III malocclusion with anterior open bite, interdental spacing in lower anterior teeth( 41, 42, 43,31,32,33,) multiple miss ing teeth, ( 16,18,35,36,37,46,48)   The haematological examination revealed that ran dom blood glucose was 136 mg % and the high blood pressure.Considering the patient's uncontrolled dia betes and hypertension, dental treatment was de ferred and he was referred to an endocrinologist for further evaluation (3) .

Discussion
Acromegaly is an acidophilic tumor that occurs after adolescence that is, after the epiphyses of the long bones have fused with the shafts, in which the person cannot grow taller, but the bones can become thicker and the soft tissues continue to grow (4) .This is a multisystem disorder due to excessive secretion of growth hormone by the somatotropic cell in the ante rior part of pituitary gland (5) .The pituitary gland is a small, bean-shaped structure that lies at the base of the brain within the confines of the sella turcica and has a central role in the regulation of most of the other endocrine glands.
Pituitary adenomas are the most common cause of pituitary hormone hyper secretion in adults.They account for approximately 15% of all intracrani al neoplasms (6) .It is most often diagnosed in middleaged adults as acromegaly and due to insidious onset and slow progression; it is often diagnosed four to more than ten years after its onset (7) .The incidence of acromegaly is approximately 5 cases per million per year and the prevalence is 60 cases per million.Over 90% of patients with acromegaly have a benign mono clonal pituitary adenoma, which are not surrounded by hyperplastic tissue.Densely granulated adenomas grow slowly and occur in patients over the age of 50.Sparsely granulated adenomas grow faster and occur in younger patients.In more than 95% of patients, the aetiology is pituitary somatotrophinoma.Somato troph adenomas are monoclonal in origin and develop from genetic changes (8) .
All the major anterior pituitary hormones, except for growth hormone, exert their principal effects by stimulating target glands.Growth hormone exerts its effects directly on all or almost all tissues of the body (4) .When their physiological level is altered due to pathological conditions, it can lead to a clinical syn drome.Pituitary adenoma is a benign neoplasm that arises from one of the five anterior pituitary cell types.The tumors arising from somatotropic cells results in hypersecretion of the growth hormone which can lead to acromegaly in adults.G-protein is a stimulatory protein that has a pivotal role in signal transduction in several endocrine organs, including the pituitary.The α-subunit of Gs (Gsα) is encoded by the GNAS1 gene, located on chromosome 20q13.A mutation in the αsubunit of the stimulatory proteins (Gsα ) that inter feres with its intrinsic GTPases activity therefore results in constitutive activation of Gsα, persistent generation of cAMP, and unchecked cellular prolifer ation state (9) .The clinical manifestation of this patho physiology results in its effect mainly on structures like bone and soft tissue.There are two principal mechanisms of bone growth.First, in response to growth hormone stimulation, the long bones grow in length at the epiphyseal cartilages, where the epiph yses at the ends of the bone are separated from the shaft.Second, osteoblasts in the bone periosteum and in some bone cavities deposit new bone on the surfaces of older bone.Simultaneously, osteoclasts in the bone remove old bone.When the rate of deposi tion is greater than that of resorption, the thickness of the bone increases.These changes are manifested as mandibular prognathism, nasal bone prominence, frontal bossing and increase in vertical height (7) .Bone mineral density is also altered in acromegaly.Cortical bone thickness (as measured by the meta carpal index and histomorphometric parameters) and its porosity is decreased.The normal trabeculaer pattern could be decreased or increased.The upper part of the body shows dorsal kyphosis and compen satory lumbar hyperlordosis.Acromegalic patients have progressive osteophytosis.The excess of GH has a deleterious effect on the joints in these patients (10) .
In our patient significant progressive mandib ular prognathism was observed.It has been postulat ed that post pubertal overproduction of GH leads to highly disproportionate growth of the jaws and facial bones, which is mainly as a result of periosteal bone apposition due to reactivation of the subcondylar zones.This result in enlargement of the ascending ramus and prominence of the mandible compared to maxilla, which is the most noticeable profile charac teristic of an acromegalic patients (11) .
As a sequlae to this mandibular growth, mac roglossia occurs which can cause flaring and spacing of teeth.A study conducted showed that, 50% of the subjects had increase in tongue size, the histology of which showed enlargement of muscle fibers espe cially anteriorly in acromegaly.Along with this, the soft palate also shows enlargement which can lead to sleep apnea.Sleep apnea is manifested as snoring and daytime sleepiness in acromegaly.The impact of respiratory complication is high in acromegaly.The impaired respiratory functions in these patients oc cur due to factors involving upper airway and bone musculature of chest and lung elasticity.Using Poly somnography, a study conducted by Attal and Chan son found an average rate of 69% for obstructive sleep apnoea in patients with active disease in pro spective and retrospective studies (12) .Types of ap noea in acromegaly were either central or obstruc tive (13,14) .

J Clin Biomed Sci 2014; 4(1):247-50
In our study, the patient also reported with sleep apnea which may be attributed to the excessive soft tissue enlargement of posterior palate.Growth is most conspicuous in soft tissues, skin, and viscera and in the bones of the face, hands, and feet.Skin thicken ing is due to glycosaminoglycan deposition and in creased collagen production by connective tissue.A Study done by Gloria Lugo, Lara Pena, et al showed, that excess GH in humans is associated with increased activity of the epithelial sodium channel, which con tributes to the volume expansion and soft tissue mani festations (15) .Pigmented skin tags are frequent and could be due to GH/IGF-I excess or arise as a conse quence of insulin resistance and dyslipidaemia and are used as a marker for colonic polyps (7,15) .
The hands and feet were also enlarged with broad sausage-like fingers.Acromegaly also affects the different organs in the system like the liver which secretes several small proteins called somatomedins.Growth hormone excess is also associated with a num ber of other disturbances, including abnormal glucose tolerance and diabetes mellitus, generalized muscle weakness, hypertension, arthritis, osteoporosis, and congestive heart failure (9,7) .
Radiographic features are striking, with the enlargement of sella turcica being the important fea ture in acromegaly patient.The other features are, prominent supraorbital ridges, hypercemoentosis, large pulp chambers, and increase in size of mandible, interdental spacing, hand and wrist, shows tufting of fingers.Patients with acromegaly usually exhibit en largement of all parts of the neuro cranium and orofa cial bones except the maxilla (5) .
Significant progress have made in the manage ment of acromegaly although there are several of limi tations.Treatment modalities include medical, sur gery and radiotherapy.Medical therapies for manage ment of acromegaly include dopaminergic agonists, somatisation analogues, and growth hormone recep tor antagonists and surgical therapy includes transsphenoidal approach and transnasal endoscopic approach frontotemporalcraniotomy (3) .Radiotherapy includes gamma knife.Remission of the tumour after a period of time is to be evaluated which can be an important factor in giving a prognosis to the treat ment.Soft tissue management is less complicated be cause after normalizing the GH, soft tissue reverses back to normal, whereas the osseous changes are not reversible and may need surgical intervention (5) .
The recurrence rate following surgical correc tion can result due to continued release of GH and varies between 20% and 38% in different studies.This view is also supported by Josef Marek and Mar tin Gosau1etal (16,17,11) who states that 1-2 % adeno ma can recur.Our patient had an uncontrolled glu cose level, a progressive mandibular lengthening, and persisting coarse facial features, all of which in dicate a persisting hypersecretion of pituitary gland which needs to be further evaluated by an endocri nologist.
The prognosis is varying in different litera ture.An article by Kinnman J shows a 6% recurrence (18) , even though, new advances in stereotactic radio therapy, gamma-knife radiotherapy, and novel thera peutic agents have improved pituitary tumor man agement 6 and despite of all the measures taken to prevent the hyper secretion of GH , a minute amount can be traced in blood after a prolong period of time, can lead to further systemic manifestation of the disease .A few reports suggest that patient with acromegaly have an increased mortality rate com pared to that of general population due to uncon trolled diabetes mellitus , hypertension which can collectively lead to ventricular dysfunction and car diac failure (19)(20)(21)(22) .

Conclusion
A case of acromegaly has been reported with its clinical and radiographic features.Acromegaly is an insidious disease with characteristic orofacial changes.Management of this disorder requires a multidisciplinary approach with a close cooperation between the various medical and dental specialities.It is important for the dental professional to familiar ise with the clinical manifestations which can aid in early detection and adequate treatment and hence reduce the mortality and morbidity of the disease.
carious teeth( 45,) and poor oral hygiene.A diagnosis of Angle's class-III malocclusion with anterior open bite associated with acromegaly was considered 9 as shown in Fig 1.The patient was subjected to radiographic examination which included lateral Cephalograph, orthopantomo graph, skull view, and hand and wrist view.Lateral Ceph revealed mandibular prognathism, marked sella turcica enlargement with steepening of angle of mandible.OPG showed hypercemoentosis (36, 37, and 46, 47) and multiple missing teeth.PA showed thickening of the border of skull, and hand wrist showed tufting of fingers as shown in Fig 2.