GIGANTISM,AND OTHER ENDOCRINE DISEASES OF BONE

ENDOCRINE BONE DISEASES

DR. ARIF KHAN S

INTRODUCTION

• Thyroid disorders

• Growth hormone disorders

• Gonadal disorders

• Hypercortisolism

• Other disorders ;

HYPOTHYROIDISM

• deficiency of the thyroid hormones thyroxine and triiodothyronine,

during fetal life (cretinism)

early childhood (juvenile myxedema or juvenile hypothyroidism)

Adultdhood (myxoedema, hypothyroidism)

DISEASE ETIOLOGY

• primary, caused by disease of the thyroid gland,

• secondary, caused by lack of thyroid-stimulating hormone (TSH) produced by the pituitary gland

• Due to the popularity of congenital hypothyroidism screening programmes, the untreated congenital hypothyroid patient is a rarity.

• juvenile hypothyroidism, where thyroid hormone becomes inadequate in childhood or adolescence, after the brain development is complete, is more common.

• Early autoimmune destruction of the thyroid gland is the commonest cause while cases due to iodine deficiency are also being reported

• The major target sites are the growth plates and epiphyses, best-demonstrated in the hands and the hips

• Effects of thyroid hormone levels on a growing skeleton, after formation of epiphysis is less

• The key symptoms and signs include lethargy, constipation, an enlarged tongue, abdominal distention, and dry skin

• Usg has an important role in diagnosing fetal hypothyroidism

Can be demonstrated as absent or small non ossified distal femoral or proximal tibial epiphyses .

Some cases with epiphyseal dysegnesis.

• fundamental radiographic feature in both forms of hypothyroidism is delayed skeletal maturation with stunting of bone growth leading to dwarfism

• the appearance of the secondary ossification centers is greatly delayed

• Epiphyses ossify from numerous ossification centers, thereby acquiring a fragmented appearance and on occasion appearing abnormally dense

• Underpneumatization of the sinuses and mastoids are also typical radiographic findings associated with hypothyroidism

• Complications

One of the common complications of hypothyroidism is the development of slipped femoral capital epiphysis.

HYPERTHYROIDISM

• in 1891 when von Recklinghausen described the "worm eaten" appearance of the long bone

• With the introduction of antithyroid drugs and radioiodine in the 1940s, clinically apparent hyperthyroid bone disease became less common

• that bone loss is common in patients with overt hyperthyroidism and to a lesser extent in those with subclinical hyperthyroidism.

• Most evident bone finding is osteoporosis but clinically less apparent unless in advanced stages

THYROID ASSOSCIATED ORBITOPATHY• Most common cause of proptosis in adults, frequently assosciated with grave’s

disease

• thyroid associated orbitopathy is characterised by enlargement of the extraocular muscles (EOMs) as well as increase in the orbital fat volume

• antibodies to thyroid stimulating hormone (TSH) appear to cross react with antigens in the orbit resulting in infiltration by activated T lymphocytes, with subsequent release of inflammatory mediators.

• The muscles are infiltrated with inflammatory cells (lymphocytes, macrophages, plasma cells and eosinophils), and increased mucopolysccaride deposition

• long standing cases increased collagen deposition leads to fibrosis

• increase in orbital fat volume is as a result of venous congestion (compression of superior ophthalmic vein by enlarged muscles) and / or intrinsic inflammation.

• Bilateral and symmetrical involvement is typical

• d/Ds

• orbital pseudotumour

• orbital sarcoidosis

• orbital lymphoma

• orbital metastases

• orbital amyloidosis

• Erdheim Chester disease

ACROMEGALY (HYPERPITUITARISM)

• Acromegaly is the result of excessive growth hormone (GH) production, most commonly from an adenoma of the pituitary.

• commonly affects adults in middle age and can result in severe disfigurement, serious complicating conditions, and premature death.

The most common target sites of acromegaly

JAWS

FRONTAL BONE SINUSES

SAMLL BONES OF HAND AND FEET

SPINE

CLINICAL PRESENTATION• It has both an insidious onset and slow progression and,

• diagnosed when the external features, especially of the face, become noticeable.

• soft tissue swelling visibly resulting in enlargement of the hands, feet, nose, lips and ears, and a general thickening of the skin

• generalised expansion of the skull at the fontanelle

• pronounced brow protrusion, often with ocular distension

• pronounced prognathism with attendant macroglossia and gaping teeth

• hypertrichosis, hyperpigmentation, and hyperhidrosis may occur in these patients

PATHOLOGY

• Over 90% of cases are the result of a pituitary macroadenoma. Expansion into the sella turcica may result in compression of surrounding structures, most importantly, the optic chiasma. The majority of pituitary tumours are incidental and do not have a genetic component.

• The remaining 10% of cases are the result of other tumours of the pancreas, lungs or adrenal glands that release GH

• A very small number of cases result from the excessive use of exogenous GH in atheletes.

• Serology shows: elevated levels of

1. growth hormone

2. IGF-1

Skull

Calvarial thickening, enlarged sinuses and an enlarged sella turcica. Prognathic jaw

Hands

• Terminal phalangeal tufts become hypertrophied and have a "spade appearance" which is called spade phalanx sign.

• The heads of the metacarpals are enlarged, and irregular bony thickening along the margins, simulating osteophytes, may be seen

• Joint spaces may be minimally enlarged. Premature osteoarthritis can set in the advanced stages of acromegaly.

• the sesamoid index: determined by the height and width of this ossicle measured in millimetres, if greater than 30 in women and greater than 40 in men suggest acromegaly

• Feet

Heel pad thickness may be increased (more than 25 mm)

• Spine

Lateral radiograph demonstrates posterior vertebral scalloping, a phenomenon apparently caused by bone resorption.

HYPOPITUITARISM

• Hypopituitarism refers to a condition in which there is partial or complete insufficiency of pituitary hormone secretion.

• The most common pituitary hormone deficiency, growth hormone deficiency (GHD), is the main focus of this section.

• Adult and pediatric disease spectrum completely differs

In pediatric patients can be divided into two categories: congenital and acquired

In adults, most patients have pituitary disease caused by a pituitary tumor, surgery, or radiation therapy for the tumor.

Other causes include trauma and infiltrative diseases

• Congenital causes

central nervous system tumors (e.g., craniopharyngioma, metastatic carcinoma, pituitary adenoma, pituitary carcinoma, meningioma),

central nervous system malformations,

pituitary hypoplasia or aplasia,

empty sella syndrome

• Acquired causes

• cranial irradiation

• infection (e.g., tuberculosis, fungal, abscess),

• infiltrative diseases (e.g., sarcoidosis, hemochromatosis and leukemia)

• trauma, and hypoxic insult.

PATHOLOGY

• Any disease process affecting the pituitary gland or infundibular stalk can affect the pituitary’s secretion of growth hormones along with other pituitary hormones.

• Trauma causing transection of the infundibular stalk will prevent GH-releasing hormone and other neuropeptide-releasing hormones produced in the hypothalamus from reaching the pituitary gland.

• Cranial irradiation can lead to panhypopituitarism.

CLINICAL PRESENTATION

• The radiographic manifestation for hypopituitarism is nonspecific.

• The skeletal findings in children include delayed skeletal growth and maturation, delayed appearance and growth of ossification centers as well as delayed fusion and disappearance of the ossification center, delayed dental eruptions, and osteopenia.

• The skeletal findings in adults are nonspecific and mainly consist of osteoporosis with increased incidence of fracture.

DWARFISM

• dwarfism is defined as an adult height of less than 4 feet 10 inches

• Proportionate and disproportionate.

• Growth hormone deficiency typically leads to proportionate dwarfism.

• Children affected will show slow gain in height and will be smaller than normal children of the same age group.

HYPOGONADISM

• Primary : deficient production of sex hormones from gonada.

• Secondary: low production of gonadotropins ( LH, FSH) from pituitary or GnRH from hypothalamus.

Primary when present with normal genetic karyotype its referred to as Eunuchoidism

In older women , deficiency seen assosciated withmenopause.

In younger women its seen associated with TURNER’s SYNDROME

RADIOLOGICAL FINDINGS

• Generalized decrease in bone density.

• Delay in skeletal maturation which manifests as delayed closure of epiphyses

Results in long extremities with short trunk.

TURNER’S SYNDROME

• the most common of sex chromosome abnormalities in females.

• Karyotype 44-XO

• estimated at ≈ 1 : 2000 - 5000 of live birth.

• Usually presents as primary Amenorrhoea.

• Serology may show serum alpha feto protein (AFP) : decreased

beta HCG : 

elevated if hydrops present

decreased if no hydrops

serum inhibin :

elevated if hydrops present

absent if hydrops absent

INTRA UTERINE ULTRASOUND FINDINGS

• • cystic hygroma : may appear septated : one of the most typical features of Turner syndrome

• •increased nuchal thickness

• •increased nuchal translucency

• • coarctation of the aorta : 15 - 20%

• •bicuspid aortic valve

• • horseshoe kidney / pelvic kidney

• •mild IUGR

• •features related to complicating hydrops fetalis

• •short fetal limbs

POST PARTUM TO ADULTHOOD FINDINGS• Us g show streaky ovary and or Uterus.

• MSK FINDINGS :

• •scoliosis

• •short 4th metacarpal : positive metacarpal sign

• •narrowing scapho-lunate angle : positive carpal sign

• •abnormal medial femoral condyle

• •decreased carpal angle : Madelung deformity

• •short stature

• •webbed neck

• •valgus deformity of elbow : increased carrying angle - cubitus valgus

HYPERGONADISM

• Overproduction of sex hormones by testes or ovaries.

• Pathology usually involves high ACTH secretion

Deficiency in cortisol high ACTH indirect excessive of sex steroids (adrenals)

Or

CNS lesion Increase GnRH hypergonadism

Both are central.

• Skeletal manifestations

• Precocious growth and maturation

• Epiphyseal ossification centers appear nearly.

• Long bones grow rapidly and the growth and growth plates close early.

• Short stature* (tall childbecoming short adult )

• Morphology of skeleton is otherwise normal.

HYPERCORTISOLISM

• Exposure to excessive corticosteroids (gluco corticoids)

• Causes :

Central: increased ACTH

Peripheral : increased corticosteroid production due to Adrenal tumors

( adenomas, carcinoma) , Ectopic ACTH producing tumors (bronchial

carcinoma)

Iatrogenic: treatment with corticosteroids

aka CUSHING’s SYNDROME.

• Effects of Glucocorticoids in bones:

• Inhibition of new bone formation

• Stimulation of bone resorption by osteoclast

• Decrease intestinal absorption of calcium

• Increase renal excretion of calcium

• Decrease synthesis of collagen

Results in osteoporosis, osteonecrosisand muscle wastng.

Big but weak

Hypercortisolism during skeletal immaturity suppresses growth

Results in short child with osteoporosis.

Osteonecrosis at epiphyses leads to early degenerative Osteoarthropathy

• Radiological features:

1. Osteoporosis is generalized ; particularly involves spine , pelvis and ribs.

2. Biconcave fish like vertebral bodies; central EP depressions with accentuationof primary trabeculae

3. Marginal condensation at the Eps

4. Exuberant callus may be seen in long bones ribs

• Although vertebral sclerosis with osteoporosis is typical , insdistinguishable from other causes of osteoportic spine like

Hyperthyroidism

Hyperparathyroidism‘

hypogonadism

FAMILIAL IDIOPATHIC HYPERPHOSPHATASIA

• rare autosomal-recessive disorder

• affecting young children, generally within their first 18 months

• associated with progressive bone deformities

• often referred to as “juvenile Paget disease,”

• SYNONYMS: familial osteoectasia ;hyperostosis corticalis deformans juvenilis

• Clinically, it is characterized by

painful bowing of the limbs,

muscular weakness, abnormal gait,

pathologic fractures, spinal deformities,

loss of vision and hearing,

• SEROLOGY : elevation of serum alkaline phosphatase, increase in the

amount of leucine aminopeptidase.

marked thickening of the cortex of the humerus and coarsening

of the bony trabeculae, resembling pagetic bone

hands shows sclerotic changes in the bones and a marked narrowing of the medullary

cavity of the metacarpals and phalanges

bowing of the long bones of the lower extremity, a striking feature of familial

idiopathic hyperphosphatasia

thickening of the tables and a “cotton ball” appearance

of the cranial vault, similar to that of Paget disease

the coarse trabecular pattern and cortical thickening typical of this

condition..

GAUCHER DISEASE

• Ffamilial inherited disease of unknown cause.

• Transmitted as an autosomal-recessive trait.

• abnormal deposition of cerebrosides (glycolipids) in the reticuloendothelial cells of the spleen, liver, and bone marrow(accumulates within the macrophages).

• The disease results from numerous mutations at the genetic locus encoding the enzyme glucocerebrosidase that lead to the defective activity of lysosomal hydrolase.

• The presenting clinical features of patients depend on the type of disease they have

• The adult form of the disorder (type I) is the most common and typically presents with abdominal distention secondary to splenomegaly

• Three types

• There is a diffuse osteoporosis that is frequently associated with medullary expansion. In the ends of the long bones, this phenomenon is referred to as the “Erlenmeyer flask” deformity .

• d/ds

• Niemann-Pick disease

• Fibrous dysplasia

• Sickle-cell anemia

• Thalassemia

• Ollier disease (enchondromatosis)

• Pycnodysostosis

• Lead poisoning

• Localized bone destruction assuming a honeycomb appearance is also typically seen ;

• gross osteolytic destruction is usually limited to the shafts of the long bones.

• Moreover, sclerotic changes are common, occurring secondary to a repair process or bone infarctions

• Medullary bone infarction and a periosteal reaction may lead to a bone-within-bone phenomenon, which may resemble osteomyelitis

• Osteonecrosis especially of the femoral heads Is a common complication of GAUCHER’S

SPOTTERS

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