Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5210_Библиотеки_им_академика_М_И_Перельмана
.pdf
(a) (b)
Figure9.1 (a) The facial appearance of a child with an accumulation of oedema in the setting of
hypothyroidism. (b) Same patient after treatment with hormone therapy. Source: Reproduced with
permission from Elsevier.
111
Hypothyroidism in children is stratified into congenital thyroid agenesis, which is most likely
seen in Down and Turner syndromes, ultimately progressing into cretinism. The annual incidence
is ~ 1in 4000newborns(19). They typically present with mental and physical retardation, bradycardia, dyspnea, large head, short neck, hypertelorism, flat nasal bridge, loss of facial expression
and thick textured skin(18, 20). Puffy face is a characteristic feature of hypothyroidism in children
(Figure9.1).
In contrast, adulthood hypothyroidism is diagnosed more in women, with a prevalence rate of
~5% in the United States of America, out of which ~0.5% of patients present with clinical validation(21, 22). They present with overweight, dysregulated respiratory rate and myxedema (accumulation of subcutaneous polysaccharides), which may evolve into myxedematous crisis, a possibly
fatal condition involving multiple organ system failure(23). One of the most reliable tests for hypothyroidism includes circulating TSH, T4 and T3 levels (24). Other supplemental investigations
include ultrasound and other imaging modalities with or without radioactive tracer. Treatment
involves synthetic thyroid hormones such as levothyroxine(23). Craniofacial features of hypothyroidism are listed in Table9.2.
9.6.2 Hyperthyroidism
Hyperthyroidism is characterised by increased circulating plasma levels of thyroid hormones due to
hyperactivity of the thyroid gland. The aetiology is multifactorial within the exogenous and endogenous realm. The use of a particular class of medications (anti- arrhythmic or potassium channel
blockers) and beyond physiologic levels of synthetic thyroid hormone are contributors toGrave’s
disease, toxic nodular goitre and post- partum thyroiditis(25). The annual incidence ofGraves’s disease is ~0.5% cases per 1000 people, and goitre constitutes about ~20% of thyrotoxicosis(26).
t.me/Dr_Mouayyad_AlbtousH
112
Table9.2 Craniofacial manifestations ofhypo andhyperthyroidism.
Hypothyroidism Hyperthyroidism
Swelling of the face (myxedema) Engorged thyroid
Thick dry skin Extra glandular lingual thyroid
Hoarseness of voice Exophthalmos
Micrognathia (underdeveloped condyle and
mandible)
Enamel hypoplasia Periodontal disease
Delayed eruption Osteoporosis (maxillary and mandibular)
Macroglossia, glossitis, taste alteration Burning sensation
Increased consumption of sugars leads to caries
Figure9.2 Exophthalmos secondary to hyperthyroidism. Source: Reproduced with permission from
Elsevier.
Hyperthyroidism has a female predilection and occurs around peri- puberty, pregnancy and
menopause. Clinical manifestations span Grave’s orbitopathy, exophthalmos (Figure 9.2),
tachycardia, atrial fibrillation, heat intolerance, weight loss, fatigue, restlessness and erythema of
the skin involving many organ systems(11, 27). Exophthalmos is a characteristic feature of
hyperthyroidisim (Figure 9.2). Diagnosis encompasses lab values of thyroid hormones, TSH
and imaging. Treatment involves antithyroid medications such as propylthiouracil, carbimazole, steroids, radioactive iodine, beta- blockers and surgery(28, 29). Craniofacial features of
hyperthyroidism are listed in Table9.2.
9.7 Parathyroid Functions inHealth
9.7.1 Parathyroid Anatomy andPhysiology
Two pairs of small pea- sized parathyroid glands are located adjacent to the thyroid gland in the
anterior neck. Parathyroid glands secrete parathyroid hormone, a polypeptide which regulates calcium in the peripheral bloodstream by absorption and maintenance in the bones, intestines and
t.me/Dr_Mouayyad_AlbtousH
kidneys(30). It facilitates the production of vitamin D and calcitriol (1,25- dihydroxycholecalciferol
and maintains phosphorus in the proximal and distal tubules of the kidney. PTH has an impact
on bones by stimulating osteoclasts, leading to resorption, osteoblasts, and their expression of
receptor activator for nuclear factor kappa- B ligand (RANKL) to differentiate into osteocytes and
inhibits osteoprotegerin for preferential osteoclastic variation (31).
Dysregulation characterised by over or underactivity is recognised by the negative feedback
mechanism to conserve serum calcium levels. Understanding the complex mechanism of PTH is
significant in managing relevant clinical outcomes(32, 33).
9.8 Parathyroid Dysfunction andIts Oro- facial Manifestations
9.8.1 Hypoparathyroidism
Hypoparathyroidism is less common and is caused predominantly by congenital, autoimmune
conditions, injury to the parathyroid gland iatrogenically due to surgery and uncommon genetic
aberrations such as DiGeorge syndrome, hemochromatosis and thalassemia. The appropriate
prevalence of hypoparathyroidism in the United States is 0.004%(34).
Hypoparathyroidism in children is scarce. Clinical manifestations include congenital cardiac
defects, craniofacial disorders, cleft lip/palate, susceptibility to dental caries, enamel fractures and
longstanding infections. Adults tend to have cardiac arrhythmia, bronchospasm, abdominal pain,
seizures, tetany, paresthesia, alopecia and muscle cramping. Positive Chvostek indicating
hyperexcitable facial nerve and Trousseau signs are clinically effective in identifying hypocalcemia, arterial occlusion and nerve excitability. History, clinical exam, serum hormone and calcium
levels with supporting images aid in diagnosis. The most common treatment options include PTH
hormone replacement, vitamin D and calcium supplements (35). Craniofacial features of
hypoparathyroidism are listed in Table9.3.
113
9.8.2 Hyperparathyroidism
Primary hyperparathyroidism is described as elevated levels of parathyroid hormone due to hyperplasia, adenoma or rarely malignancy resulting in hypophosphatemia and hypercalcemia.
Hyperplasia isobserved in multiple endocrine neoplasias (MEN) types I and II A with tumours
Table9.3 Craniofacial manifestations ofhypo andhyperparathyroidism.
Hypoparathyroidism Hyperparathyroidism
Retarded growth of teeth/hypodontia Unilocular/multilocular radiolucency (diminished
Enamel/dentin hypoplasia/hypo calcification Loss of lamina dura
Truncated roots Easily fractured teeth
Wide pulp chambers and calcifications Widening of pulp chambers
Maxillary and mandibular exostosis Malocclusion
Orofacial paresthesia, muscle twitching Calcifications
Oral infections Brown tumours
t.me/Dr_Mouayyad_AlbtousH
mandibular bone density)
114
Figure9.3 Brown tumour in
hyperparathyroidism presenting as an
intraoral swelling in the mandible.
Source:Courtesy of Dr. Preethi Nair.
and hypercalcemia. Carcinomas and adenomas are sporadic and characterised by excessive urination, thirst, constipation, bone pain, depression, fatigue and renal calculi, commonly known as
stones, groans, bone and psychiatric moans. They are commonly treated by surgical resection.
Secondary hyperparathyroidism is most commonly detected in end- stage renal disease, vitamin
D deficiency and GI disorders. Chronic renal failure is accompanied by increased phosphate and
decreased calcium and vitamin D absorption. GI malabsorption is seen in the setting of reduced
calcium and phosphate alongside elevated levels of PTH(36).
Persistently excessive secretion of PTH following secondary hyperparathyroidism results in consequential tertiary hyperparathyroidism, which most likely follows renal transplantation and
resolves essentially(31).
Brown tumours are pathognomonic of hyperparathyroidism. They are uncommon benign osteolytic lesions owing to excessive osteoclastic activity induced by abnormal PTH production. Clinical
features include pain, swelling (Figure9.3) and pathological fracture of the bone.Radiographs
reveal the expansion of the lingual cortex, and panoramic views show radiolucencies. CT scans
show expansile lesions (Figure9.4a– c). Microscopically, multinucleated- like giant cells within connective tissue, haemorrhage, hemosiderin deposition and extravasation of RBCs are classic(37, 38).
Craniofacial features of hyperparathyroidism are listed in Table9.3.
9.9 Adrenal Functions inHealth
Adrenal glands are small endocrine glands weighing ~5– 10 g located bilaterally superior on
each kidney(39). The outer surface adrenal cortex secretes glucocorticoids (cortisol), mineralocorticoids (aldosterone) and androgens. The inner medulla secretes catecholamines (epinephrine and nor- epinephrine)(40). Aldosterone is crucial for maintaining blood pressure through
the renin- angiotensin system, extracellular fluid reabsorption of sodium and water and excretion of potassium(41). Primary functions of cortisol include metabolism, regulation of blood
glucose, lipids, and proteins, maintaining hemostasis, blood pressure, cardiovascular function,
inhibition of osteoclast and immune and stress management(42). Its anti- inflammatory actions
are contingent on inhibitory activity of leucocyte function, endothelial expression and corresponding neutrophil attraction, prostaglandin secretion, lysosome and cytokine release(43).
t.me/Dr_Mouayyad_AlbtousH
(a) (b)
(c)
Figure9.4 (a– c) Occlusal radiograph demonstrating expansion of the lingual cortex, panoramic revealing
radiolucencies of the L mandible and CT showing expansile lesion with discontinuity of lingual cortical
plate. Source: Courtesy of Dr. Preethi Nair.
115
9.9.1 Hypothalamus Pituitary Adrenal Axis (HPTA)
Like other endocrine organs, cortisol secretion is regulated by the hypothalamus– pituitary– adrenal
axis (HPAA). The hypothalamus releases corticotropin- releasing hormone (CRH) to manage diurnal rhythm as an outcome of stress. CRH triggers ACTH stimulation in response to serum cortisol
levels via a negative feedback mechanism(44). Cortisol secretion follows a circadian pattern, and
the highest serum levels are observed early in the morning(45). Optimal cortisol secretion in
24 hours is ~20 mg; however, cortisol levels increase and are disrupted during infection, neoplasm,
surgery and stress(46).
9.10 Adrenal Dysfunction andIts Oro- facial Manifestations
9.10.1 Adrenal Insufficiency
Addison’s adrenal insufficiency (AI) is outlined in primary, secondary and tertiary. Primary AI is
chiefly caused by the autoimmune destruction of the adrenal cortex, surgical removal of the adrenal gland and idiopathic infections(47). Secondary AI is most likely due to a pituitary gland
tumour leading to suppressing pituitary hormones and the HPA axis. Tertiary AI occurs as a result
of persistent administration of extrinsic systemic steroids(48). Chronic use of exogenous steroids
has been used by ~2% of adults in the United States, which justifies the rationale for tertiary
AI(49). The incidence of AI is observed to be ~1in 10,000/20,000newborns(50). ~3in 10,000 cases
are reportedly due to disrupted HPA axis.
t.me/Dr_Mouayyad_AlbtousH
(a)
(b)
116
Figure9.5 (a, b). Hyperpigmented macules of the lower lip mucosa and left buccal mucosa in the setting
of adrenal insufficiency. Source: Courtesy of Dr. Nicola Cirillo.
Clinical features of AI include overall weakness, anorexia, mental depression, nausea, vomiting, abdominal pain, myalgia, arthralgia and hyperpigmentation (bronzing) of skin and mucosa
(Figure 9.5) (51, 52). Diagnosis is established based on the serum levels of cortisol, their corresponding peptide hormones, and ACTH stimulation tests(52). Management includes monitoring
blood pressure, rehydration, and topical and extrinsic steroid supplementation. Adrenal crisis is a
debilitating life emergency that arises in patients with primary AI. It is intensified by surgery,
infection or when the demand for cortisol is unmet(53, 54).
9.10.2 Hypercortisolism
The most common cause of Cushing syndrome/hypercortisolism originates from someone being
administered external corticosteroids(55). Endogenous Cushing syndrome is less common
than AI, with an annual incidence of ~1– 2 per one million population annually(56). Patients
with Cushing syndrome classically present with muscle weakness/myopathy, osteoporosis,
bone fractures, psychosis/cognitive dysfunction, kyphosis, hypertension (cushingoid or moon
facies) (Figure 9.6), hyperglycemia, peptic ulcer, glaucoma, weight gain (Buffalo hump), hirsutism,
acne, plethoric facies, oral infections and purple– red abdominal striae (57). However, the
manifestations can be ACTH- dependent or independent. Overnight dexamethasone suppression
test, late- night salivary cortisol and 24- hour urinary- free cortisol have helped navigate towards
the diagnosis(58). Management of Cushing syndrome comprises surgical removal of adrenal or
pituitary tumours and disorders involving every organ system that impairs normal cortisol
secretion(59).
9.11 Carbohydrate Metabolism inHealth
Carbohydrate metabolism comprises biochemical events engaging the production of glucose,
breakdown, absorption into the bloodstream and utilisation by the tissues. The metabolic
pathways involve glycogenesis (production of glycogen), glycogenolysis (breakdown of glycogen), glycolysis (breakdown of glucose to pyruvate), gluconeogenesis (synthesis of glucose from a
non- carbohydrate source) and other transition reactions(60). Insulin is the prime regulator in
t.me/Dr_Mouayyad_AlbtousH
Figure9.6 Cushingoid facies secondary to
hypercortisolism. Source: Miller etal. (2018)/with
permission from Elsevier.
preserving glucose homeostasis. Insulin enhances glucose uptake in the muscle, inhibits glucose
production by the hepatocytes and decreases lipolysis (61). Dysregulation of insulin metabolism
leads to hyperglycemia and diabetes mellitus.
117
9.12 Carbohydrate Metabolism Disorders andTheir
Oro- facial Manifestations
9.12.1 Diabetes Mellitus
Diabetes mellitus (DM) is a diverse group of metabolic diseases with defects in insulin secretion,
action, or both by beta cells of pancreatic islets of Langerhans with characteristic hyperglycemia.
Approximately 38 million patients with a primary DM diagnosis visit their physician offices
globally. Over 1.5million deaths have been attributed to DM, making it the eighth leading cause of
mortality(62). Three distinct types of DM are type 1 (previously known as juvenile or insulindependent DM), type 2 (non- insulin- dependent DM) and gestational DM(63).
9.12.1.1 Type 1 DM
Type 1 DM is caused mainly by the autoimmune destruction of pancreatic beta cells after an insulin deficiency(63). Type 1 DM accounts for 5– 10% occurring in childhood and adolescence with
thin body stature and rapid clinical onset. Pathology in glucose metabolism, absorption and utilisation owing to consumption of energy sources from lipids and proteins(64). It favours an unstable disease control derived from an acute onset resulting in a severe complication of diabetic
ketoacidosis.
9.12.1.2 Type 2 DM
Type 2 DM ranges from insulin shortage to resistance with secretory dysregulation. Type 2DM
accounts for 90– 95% of the cases prevalent in middle age group(65). Risk factors include age,
t.me/Dr_Mouayyad_AlbtousH
118
genetic predisposition, lifestyle, environmental
factors and cardiovascular and renal disease comorbidities(66). Hyperglycemia is the central feature
with associated gluconeogenesis and glyco genolysis
leading to polyphagia (increased food intake), polyuria (frequent urination in the setting of increased
osmolarity) and polydipsia (increased thirst)(63).
Advanced glycation end products are vital in the
underlying pathology of DM. These are glycated
proteins or lipids resulting from glucose binding
and prolonged hyperglycemia. Increased tissue
destruction is directly proportional to the level of
hyperglycemia and its duration of exposure (67).
Complications included but are not limited to microangiopathy resulting in nephropathy and retinopathy,
long- term damage and dysfunction of cardiac and
Figure9.7 Hyposalivation and atrophic
glossitis in a patient with type 2 DM.
renal vessels from macroangiopathy, neuropathy
owing to peripheral neuropathy, frequent infections
and delayed wound healing(68, 69).
Oral manifestations include hyposalivation, oral infections such as oral candidiasis, dental
caries secondary to hyposalivation (Figure9.7), diabetic sialadenosis, periodontal disease, oral
paresthesia, taste alteration, burning mouth and dysphagia(70). Glycemic index and periodontitis have an established bidirectional link(71). The noteworthy question has been whether
periodontal infection can worsen or if periodontal treatment improves glycemic index.
Someliterature has proven reasonable diabetic control has a similar periodontal status as nondiabetic, and poor control has led to gingivitis, clinical attachment loss and periodontitis. The
background involves the production of inflammatory mediators, signalling, increased matrix
metalloproteinase (collagenase) activity, immune mediation, impaired neutrophil activity,
constant exposure to AGEs and reactive oxygen species, ultimately resulting in tissue
destruction(72– 74).
Labs based on plasma blood glucose and glycosylated haemoglobin (HbA1C) tests help understand the pattern of DM. HbA1C is the glucose bound to haemoglobin that describes the effectiveness
of long- term therapy and can be performed in a non- fasting individual(75). HbA1C above 6.5%
and plasma glucose level >180 mg/dl are deemed hyperglycemia, indicating complications(76).
Oral glucose tolerance test has also helped provide an initial diagnosis of DM and gestational
DM(77).
9.12.2 Gestational DM
This type of DM occurs during pregnancy. Approximately 2– 10% of women during pregnancy
acquire insulin resistance alongside other hormonal changes, and 60% of the women develop type
2 DM with an established diagnosis of gestational DM(77). Age, body mass index (BMI), family
history, comorbidities and oral contraceptive pills are all contributing risk factors. OGTT and
HbA1C help attain initial and manage established diagnosis. Oral hypoglycemics, in some cases of
insulin and periodic follow- up, may prevent complications such as premature labour or an overweight baby(78, 79).
t.me/Dr_Mouayyad_AlbtousH
9.13 Mucopolysaccharidosis
Chondroitin, dermatan, heparan and keratan sulfates are glycosaminoglycans (GAGs) examples(80). Mucopolysaccharidosis occurs when enzymes are deficient in metabolising one of the
GAGs(81). A diverse group of metabolic diseases is displayed in an autosomal recessive manner. They are further classified as syndromes I- H, I- S, II, III- A, III- B, IV- A, IV- B, VI conditional
on the enzyme deficiency alpha- L- iduronidase, iduronate- 2- sulfatase, heparan- N- sulfatase,
alpha- N- acetylglucosaminidase, galactose- 6- sulfatase, beta- galactosidase and arylsulfatase B,
respectively(82).
Clinical features vary depending on the type of syndrome and manifest with diminished intellectual ability, growth deficit, ocular blindness, congenital cardiac abnormalities and musculoskeletal disorders(83). Patients may present with macroglossia, gingival hyperplasia, thin enamel and
multiple impacted teeth(84).
Excessive amounts of GAGs and the deficiency of enzymes confirm the diagnosis of mucopolysaccharidosis(85). There is no specific treatment to manage mucopolysaccharidosis, and it depends
on the intellectual ability and longevity of the patient. Enzyme replacement therapy, managing
complications of another organ system, improving patient’s well- being and managing dental
abnormalities have been helpful(86).
9.14 Protein Metabolism inHealth
119
Protein metabolism denotes a cascade of events involving synthesising proteins and amino acids
by transcription, translation and protein catabolism(87). These processes involve multiple enzymes
and biochemical steps at the cellular and molecular level for energy production, growth, maturation and to meet the metabolic needs of the vital organs(88). Any discrepancy in these stages may
result in defects with clinical presentations affecting different organs.
9.15 Protein Metabolism Disorders andTheir Oro- facial Manifestations
9.15.1 Amyloidosis
Amyloidosis is a rare disease caused by abnormal amyloid buildup deposition in different organ
systems(89). Amyloidosis presents with multiple complications such as chronic infections, cutaneous involvement, multiple myeloma and systemic dissemination dependent on the organ
involved(90). This systemic disorder is classified based on the precursor protein, systemic or localised (organ- specific). Organ- limited amyloidosis is a local deposition of amyloid nodules, less likely
in the oral mucosa, with characteristic light chains(91). Systemic amyloidosis occurs in several other
forms, such as primary and myeloma- associated, secondary, hemodialysis and heriditofamilial
amyloidosis(89).
Primary and hereditary associates are observed mostly in older adults involving light chains. It
results from a dyscrasia of plasma cells and is directly related to multiple myeloma(92). Signs
and symptoms include fatigue, orthostatic hypotension, neuropathy, mucocutaneous lesions,
petechiae and hepatomegaly. Macroglossia, sporadic jaw claudication and amyloid infiltration in
salivary glands may cause xerostomia and hyposalivation(93). Whereas secondary amyloidosis is
t.me/Dr_Mouayyad_AlbtousH
120
developed due to abnormal cleavage of amyloid, resulting in chronic inflammation, tuberculosis,
osteomyelitis, rheumatic disease and inflammatory bowel disease. Major organs such as the heart,
liver, kidney, spleen and adrenal are affected(94). Dialysis- related amyloidosis occurs in the setting
of chronic dialysis patients where there is abnormal beta2- microglobulin deposition. As the name
extends, hereditary amyloidosis occurs due to gene mutations in most types with autosomal dominant inheritance(95).
Histologic analysis of oral biopsy may demonstrate deposition of eosinophilic acellular deposits
in the lamina propria in a perivascular fashion. In addition, staining using Congo red dye usually
highlights abnormal protein deposits with characteristic apple green birefringence viewed under
polarised light. This method is considered the gold standard for diagnosis of amyloid deposits(96).
Surgery, renal transplantation, medical management, genetic counselling and supportive treatment for underlying cardiac and renal conditions have been some moderately successful management modalities(97).
9.16 Lipid Metabolism inHealth
Lipid metabolism is the production and degradation of lipid molecules involving energy production
and the formation of an integral part of the cell membrane. Lipid metabolism disorders may result
in cardiovascular diseases after increased plasma levels of lipoprotein, triglycerides or inherited
storage diseases secondary to defective lipid metabolism(98).
9.17 Lipid Metabolism Disorders andTheir Oro- facial Manifestations
9.17.1 Lipid Storage Disease
It is a rare heterogeneous group of disorders with a deficiency of certain lipid enzymes, resulting
in accumulation and storage at the cellular level. It happens to store lipid molecules in the lysosomes and hence gains its name, lysosomal storage disease, for a similar reason. It is commonly
observed in Ashkenazi Jewish descent(99).
9.17.2 Gaucher Disease
Gaucher disease is the frequently occurring reticuloendothelioses due to the accumulation of
glucosylceramide in the setting of deficient glucocerebrosidase(100). It is further divided into
types 1, 2 and 3 based on the central nervous system (CNS) involvement. Patients are generally
asymptomatic due to involvement of the gene in a heterozygous fashion. Specific manifestations include bone pain and infarction due to the accumulation of lipid glucocerebroside in the
bone marrow replacing hematopoietic cells. Abnormal collection in the spleen and liver affects the
reticuloendothelial system and neurologic deficit from CNS involvement(101). Oral manifestations include reduced salivary flow, mucosal pigmentation, increased risk for oral infections,
lymph node involvement, increased bleeding tendency and dental caries. There is radiographic
evidence of thinning of cortices and loss of trabeculation, obliteration of the inferior alveolar
canal, and honey- combed radiolucencies of the mandible (102). Genetic counselling and
enzyme replacement have been effective yet expensive choices. Cost- effective treatment choices
are still under review(103).
t.me/Dr_Mouayyad_AlbtousH
Соседние файлы в папке Библиотека им академика М.И. Перельмана